Many patients admitted to inpatient psychiatric hospitals present with delusions; however, the Capgras delusion is a rare type that often appears as a sequela of certain medical and neurologic conditions.¹ The Capgras delusion is a condition in which a person believes that either an individual or a group of people has been replaced by doubles or imposters.

In 1923, French psychiatrist Joseph Capgras first described the delusion. He and Jean Reboul-Lachaux coauthored a paper on a 53-year-old woman. The patient was a paranoid megalomaniac who “transformed everyone in her entourage, even those closest to her, such as her husband and daughter, into various and numerous doubles.”² She believed she was famous, wealthy, and of royal lineage. Although 3 of her children had died, she believed that they were abducted, and that her only surviving child was replaced by a look-alike.^2,3 Although the prevalence of such delusions in the general population has not been fully studied, a psychiatric hospital in Turkey found a 1.3% prevalence (1.8% women and 0.9% men) in 920 admissions over 5 years.⁴

The Capgras delusion is one of many delusions related to the misidentification of people, places, or objects; these delusions collectively are known as delusional misidentification syndrome (DMS).^5,6 The Fregoli delusion involves the belief that several different people are the same person in disguise. Intermetamorphosis is the belief that an individual has been transformed internally and externally to another person. Subjective doubles is the belief that a doppelganger of the afflicted person exists, living and functioning independently in the world. Reduplicative paramnesia is the belief that a person, place, or object has been duplicated. A rarer example of DMS is the Cotard delusion, which is the belief that the patient himself or herself is dead, putrefying, exsanguinating, or lacking internal organs.

The most common of the DMS is the Capgras delusion. One common presentation of Capgras delusion involves the spouse of the patient, who believes that an imposter of the same sex as their spouse has taken over his or her body. Rarer delusions are those in which a person misidentifies him or herself as the imposter.^3,5,6

Case Presentation

This case involved a 24-year-old male veteran who had received a wide range of mental health diagnoses in the past, including major depressive disorder (MDD) with psychotic features, generalized anxiety disorder, cannabis use disorder, adjustment disorder, and borderline personality disorder. He also had a medical history related to a motor vehicle accident with subsequent intestinal rupture and colostomy placement that had occurred a year and a half prior to presentation. He had no history of brain trauma.

The patient voluntarily presented to the hospital for increased suicidal thoughts and was admitted voluntarily for stabilization and self-harm prevention. He stated that “I feel everything is unreal. I feel suicidal and guilt” and endorsed a plan to either walk into traffic or shoot himself in the head due to increasingly distressing thoughts and memories. According to the patient, he had reported to the police that he raped his ex-girlfriend a year previously, although she denied the claim to the police.

The patient further disclosed that he did not believe his mother was real. “Last year my sister told me it was not 2016, but it was 2022,” he said. “She told me that I have hurt my mother with a padlock—that you could no longer identify her face. I don’t remember having done this. I have lived with her since that time, so I don’t think it’s really [my mother].” He believed that his mother was replaced by “government employees” who were sent to elicit confessions for his behavior while in the military. He expressed guilt over several actions he had performed while in military service, such as punching a wall during boot camp, stealing “soak-up” pads, and napping during work hours. His mother was contacted by a staff psychiatrist in the inpatient unit and denied that any assault had taken place.

The patient’s psychiatric review of systems was positive for visual hallucinations (specifically “blurs” next to his bed in the morning that disappeared as he tried to touch them), depressed mood, anxiety, hopelessness, and insomnia. Pertinent negatives of the review of systems included a denial of manic symptoms and auditory hallucinations. For additional details of his past psychiatric history, the patient admitted that his motor vehicle accident, intestinal rupture, and colostomy were the result of his 1 suicide attempt a year and a half prior after a verbal dispute with the same ex-girlfriend that he believed he had raped. After undergoing extensive medical and surgical treatment, he began seeing an outpatient psychiatrist as well as attending substance use counseling to curtail his marijuana use. He was prescribed a combination of duloxetine and risperidone as an outpatient, which he was taking with intermittent adherence.

Regarding substance use, the patient admitted to using marijuana regularly in the past but quit completely 1 month prior and denied any other drug use or alcohol use. He reported a family history of a sister who was undergoing treatment for bipolar disorder. In his social history, the patient disclosed that he was raised by both parents and described a good childhood with a life absent of abuse in any form. He was single with no children. Although he was unemployed, he lived off the funds from an insurance settlement from his motor vehicle accident. He was living in a trailer with his brother and mother. He also denied having access to firearms.

The patient was overweight, neatly groomed, had good eye contact, and was calm and cooperative. He seemed anxious as evidenced by his continuous shaking of his feet; although speech was normal in rate and tone. He reported his mood as “depressed and anxious” with congruent and tearful affect. His thought process was concrete, although his thought content contained delusions, suicidal ideation, and paranoia. He denied any homicidal thoughts or thoughts of harming others. He did not present with any auditory or visual hallucinations. Insight and judgment were poor. The mental status examination revealed no notable deficits in cognition.

The patient’s differential diagnosis included schizophreniform disorder, exacerbation of MDD with psychotic features, and the psychotic component of cannabis use disorder. His outpatient risperidone and duloxetine were not restarted. Aripiprazole 15 mg daily was prescribed for his delusions, paranoia, and visual hallucinations. The patient also received a prescription for hydroxyzine 50 mg every 6 hours as needed for anxiety.

Because of the nature of his delusions, comorbid medical and neurologic conditions were considered. Neurology consultation recommended a noncontrast head computer tomography (CT) scan and an electroencephalogram (EEG). Laboratory workup included HIV antibody, thyroid panel, chemistry panel, complete blood count, hepatitis B serum antigen, urine drug screen, hepatitis C virus, and rapid plasma reagin. All laboratory results were benign and unremarkable, and the urine drug screen was negative. The noncontrast CT revealed no acute findings, and the EEG revealed no recorded epileptiform abnormalities or seizures.

Throughout his hospital course, the patient remained cooperative with treatment. Three days into the hospitalization, he stated that he believed the entire family had been replaced by imposters. He began to distrust members of his family and was reticent to communicate with them when they attempted to contact him. He also experienced fragmented sleep during his hospital stay, and trazodone 50 mg at bedtime was added.

After aripiprazole was increased to 20 mg daily on hospital day 2 and then to 30 mg daily on hospital day 3 due to the patient’s delusions, he began to doubt the validity of his beliefs. After showing gradual improvement over 6 days, the patient reported that he no longer believed that those memories were real. His sleep, depressed mood, anxiety, and paranoia had markedly improved toward the end of the hospitalization and suicidal ideation/intent resolved. The patient was discharged home to his mother and brother after 6 days of hospitalization with aripiprazole 30 mg daily and trazodone 50 mg at bedtime.

Discussion

The Capgras delusion can present in several different contexts. A psychiatric differential diagnosis includes disorders in the schizophrenia spectrum (brief psychotic disorder, schizophreniform disorder, and schizophrenia), schizoaffective disorder, delusional disorder, and substance-induced psychotic disorder. In addition to psychiatric disorders, the Capgras delusion has been shown to occur in several medical conditions, which include stroke, central nervous system tumors, subarachnoid hemorrhage, vitamin B12 deficiency, hepatic encephalopathy, hypothyroidism, hyperparathyroidism, epilepsy, and dementia.^1,2,4,7

A 2007 retrospective study by Josephs examined 47 patients diagnosed with the Capgras delusion from several tertiary care centers. Of those patients, 38 (81%) had a neurodegenerative disease, most commonly Lewy body dementia (LBD).¹ In his review of the Josephs study, Devinsky proposed that the loss of striatal D2 receptors in LBD may be implicated in the manifestation of Capgras delusions.² The data suggest multiple brain regions may be involved, including the frontal lobes, right temporal lobe, right parietal lobe, parahippocampus, and amygdala.^1,2 Most patients in the Josephs study demonstrated global atrophy on imaging studies. One hypothesis is that it is the disconnection of the frontal lobe to other brain regions that may be implicated.^1,2,4 This results in intact recognition of facial features of familiar people, impaired emotional recognition, and impaired self-correction due to executive dysfunction.

Methamphetamine also has been implicated in a small number of cases of Capgras; the proposed mechanism involves dopaminergic neuronal impairment/loss.^1,2 Additionally, Capgras delusions have been described in cases of patients treated with antimalarial medications, such as chloroquine.⁸ Younger patients with the Capgras delusion were more likely to have purely psychiatric comorbidities—such as schizophrenia, substance-induced psychosis, or schizoaffective disorder—as opposed to underlying medical conditions.¹ In the case presented here, the Capgras delusion was thought to be due to a disorder in the schizophrenia spectrum, specifically schizophreniform disorder.

Because an increasing amount of evidence indicates that the Capgras delusion is associated with certain medical conditions, a workup should be performed to rule out underlying medical etiology. Of note, no official guidelines for the workup have been produced for the Capgras delusion. However, the workup may include brain imaging, such as magnetic resonance imaging and/or CT scan to rule out mass lesions, vascular malformations, stroke, or neuro-infectious processes; laboratory tests, such as vitamin B12, liver panel, HIV, rapid plasma reagin, hepatitis B and C viruses, parathyroid hormone levels, urine drug screen, and thyroid panel can be ordered to rule out other medical causes.^1,2,6,7,9

Consultations with internal medicine and neurology departments may be beneficial. Although treatment of the underlying condition may lead to an improvement in the symptoms, full remission in all cases has not been consistently demonstrated in the current literature.^5,7,9,10 Patients with the Capgras delusion are challenging to treat, because their delusions have been shown to be refractory to antipsychotic therapy. However, antipsychotics are currently the mainstay of treatment. Some case studies have shown efficacy with pimozide, tricyclic antidepressants, and mirtazapine.^6,9

One case study in 2014 in India of a 45-year-old woman who believed her husband and son were replaced by imposters out to kill her, showed a 40% to 50% reduction of paranoia, irritability, and suspicious scanning behaviors with a combination of risperidone and trihexyphenidyl. Despite the improvements, the woman continued to have delusions.⁷

A notable feature associated with those experiencing the Capgras delusion is the increased risk of violent behaviors, often because of suspiciousness and paranoia. A 2004 review suggested the risk of violence and homicidality is much higher in male patients compared with that of female patients with the Capgras delusion.⁹ This is despite evidence suggesting that the prevalence of the Capgras delusion seems to be greater in women.^6,9 Moreover, patients often demonstrated social withdrawal and self-isolation prior to violent acts. The victims often were family members or those who live with the patient, which is consistent with the evidence that those most familiar to patients are more likely to be misidentified.^1,2,7,9,10

A 1989 case series that examined 8 cases of the Capgras delusion listed the following violent behaviors: shot and killed father, pointed knife at mother, held knife to mother’s throat, punched parents, threatened to stab husband with scissors, nonspecifically threatened physical harm to family, injured mother with axe, and threatened to stab son with knife and burn him. Seven of the 8 patients lived with the misidentified persons, and 5 of the 8 patients were treatment resistant. The study posited that chronicity of the delusion, content of the delusion, and accessibility of misidentified persons seemed to increase the risk of violent behaviors. These authors went on to suggest that despite the appearance of stability, patients may react violently to minute changes.¹⁰ Overall literature seems to suggest the importance of performing a violence and homicidality assessment with special attention to assessment for themes of hostility toward misidentified individuals.^9,10

Conclusion

The Capgras delusion is an uncommon symptom associated with varied psychiatric, medical, iatrogenic, and neurologic conditions. Treatment of underlying medical conditions may improve or resolve the delusions. However, in this case, the patient did not seem to have any underlying medical conditions, and it was thought that he may have been experiencing a prodrome within the schizophrenia spectrum. This is consistent with the literature, which suggests that those with the delusions at younger ages may have a psychiatric etiology.

Although this patient was responsive to aripiprazole, the Capgras delusion has been known to be resistant to antipsychotic therapy. It is worth considering a medical and neurologic workup with the addition of a psychiatry referral. Further, while the patient in the presented case had the delusion that he had assaulted his mother, whom he misidentified as an imposter, the patient did not demonstrate any hostility and denied thoughts of harming her. However, given the increased risk of violence in patients with the Capgras delusion, a homicidality and violence assessment should be performed. While further recommendations are outside the scope of this article, the provider should be cognizant of local duty-to-warn and duty-to-protect laws regarding potentially homicidal patients.

Many patients admitted to inpatient psychiatric hospitals present with delusions; however, the Capgras delusion is a rare type that often appears as a sequela of certain medical and neurologic conditions.¹ The Capgras delusion is a condition in which a person believes that either an individual or a group of people has been replaced by doubles or imposters.

In 1923, French psychiatrist Joseph Capgras first described the delusion. He and Jean Reboul-Lachaux coauthored a paper on a 53-year-old woman. The patient was a paranoid megalomaniac who “transformed everyone in her entourage, even those closest to her, such as her husband and daughter, into various and numerous doubles.”² She believed she was famous, wealthy, and of royal lineage. Although 3 of her children had died, she believed that they were abducted, and that her only surviving child was replaced by a look-alike.^2,3 Although the prevalence of such delusions in the general population has not been fully studied, a psychiatric hospital in Turkey found a 1.3% prevalence (1.8% women and 0.9% men) in 920 admissions over 5 years.⁴

The Capgras delusion is one of many delusions related to the misidentification of people, places, or objects; these delusions collectively are known as delusional misidentification syndrome (DMS).^5,6 The Fregoli delusion involves the belief that several different people are the same person in disguise. Intermetamorphosis is the belief that an individual has been transformed internally and externally to another person. Subjective doubles is the belief that a doppelganger of the afflicted person exists, living and functioning independently in the world. Reduplicative paramnesia is the belief that a person, place, or object has been duplicated. A rarer example of DMS is the Cotard delusion, which is the belief that the patient himself or herself is dead, putrefying, exsanguinating, or lacking internal organs.

The most common of the DMS is the Capgras delusion. One common presentation of Capgras delusion involves the spouse of the patient, who believes that an imposter of the same sex as their spouse has taken over his or her body. Rarer delusions are those in which a person misidentifies him or herself as the imposter.^3,5,6

Case Presentation

This case involved a 24-year-old male veteran who had received a wide range of mental health diagnoses in the past, including major depressive disorder (MDD) with psychotic features, generalized anxiety disorder, cannabis use disorder, adjustment disorder, and borderline personality disorder. He also had a medical history related to a motor vehicle accident with subsequent intestinal rupture and colostomy placement that had occurred a year and a half prior to presentation. He had no history of brain trauma.

The patient voluntarily presented to the hospital for increased suicidal thoughts and was admitted voluntarily for stabilization and self-harm prevention. He stated that “I feel everything is unreal. I feel suicidal and guilt” and endorsed a plan to either walk into traffic or shoot himself in the head due to increasingly distressing thoughts and memories. According to the patient, he had reported to the police that he raped his ex-girlfriend a year previously, although she denied the claim to the police.

The patient further disclosed that he did not believe his mother was real. “Last year my sister told me it was not 2016, but it was 2022,” he said. “She told me that I have hurt my mother with a padlock—that you could no longer identify her face. I don’t remember having done this. I have lived with her since that time, so I don’t think it’s really [my mother].” He believed that his mother was replaced by “government employees” who were sent to elicit confessions for his behavior while in the military. He expressed guilt over several actions he had performed while in military service, such as punching a wall during boot camp, stealing “soak-up” pads, and napping during work hours. His mother was contacted by a staff psychiatrist in the inpatient unit and denied that any assault had taken place.

The patient’s psychiatric review of systems was positive for visual hallucinations (specifically “blurs” next to his bed in the morning that disappeared as he tried to touch them), depressed mood, anxiety, hopelessness, and insomnia. Pertinent negatives of the review of systems included a denial of manic symptoms and auditory hallucinations. For additional details of his past psychiatric history, the patient admitted that his motor vehicle accident, intestinal rupture, and colostomy were the result of his 1 suicide attempt a year and a half prior after a verbal dispute with the same ex-girlfriend that he believed he had raped. After undergoing extensive medical and surgical treatment, he began seeing an outpatient psychiatrist as well as attending substance use counseling to curtail his marijuana use. He was prescribed a combination of duloxetine and risperidone as an outpatient, which he was taking with intermittent adherence.

Regarding substance use, the patient admitted to using marijuana regularly in the past but quit completely 1 month prior and denied any other drug use or alcohol use. He reported a family history of a sister who was undergoing treatment for bipolar disorder. In his social history, the patient disclosed that he was raised by both parents and described a good childhood with a life absent of abuse in any form. He was single with no children. Although he was unemployed, he lived off the funds from an insurance settlement from his motor vehicle accident. He was living in a trailer with his brother and mother. He also denied having access to firearms.

The patient was overweight, neatly groomed, had good eye contact, and was calm and cooperative. He seemed anxious as evidenced by his continuous shaking of his feet; although speech was normal in rate and tone. He reported his mood as “depressed and anxious” with congruent and tearful affect. His thought process was concrete, although his thought content contained delusions, suicidal ideation, and paranoia. He denied any homicidal thoughts or thoughts of harming others. He did not present with any auditory or visual hallucinations. Insight and judgment were poor. The mental status examination revealed no notable deficits in cognition.

The patient’s differential diagnosis included schizophreniform disorder, exacerbation of MDD with psychotic features, and the psychotic component of cannabis use disorder. His outpatient risperidone and duloxetine were not restarted. Aripiprazole 15 mg daily was prescribed for his delusions, paranoia, and visual hallucinations. The patient also received a prescription for hydroxyzine 50 mg every 6 hours as needed for anxiety.

Because of the nature of his delusions, comorbid medical and neurologic conditions were considered. Neurology consultation recommended a noncontrast head computer tomography (CT) scan and an electroencephalogram (EEG). Laboratory workup included HIV antibody, thyroid panel, chemistry panel, complete blood count, hepatitis B serum antigen, urine drug screen, hepatitis C virus, and rapid plasma reagin. All laboratory results were benign and unremarkable, and the urine drug screen was negative. The noncontrast CT revealed no acute findings, and the EEG revealed no recorded epileptiform abnormalities or seizures.

Throughout his hospital course, the patient remained cooperative with treatment. Three days into the hospitalization, he stated that he believed the entire family had been replaced by imposters. He began to distrust members of his family and was reticent to communicate with them when they attempted to contact him. He also experienced fragmented sleep during his hospital stay, and trazodone 50 mg at bedtime was added.

After aripiprazole was increased to 20 mg daily on hospital day 2 and then to 30 mg daily on hospital day 3 due to the patient’s delusions, he began to doubt the validity of his beliefs. After showing gradual improvement over 6 days, the patient reported that he no longer believed that those memories were real. His sleep, depressed mood, anxiety, and paranoia had markedly improved toward the end of the hospitalization and suicidal ideation/intent resolved. The patient was discharged home to his mother and brother after 6 days of hospitalization with aripiprazole 30 mg daily and trazodone 50 mg at bedtime.

Discussion

The Capgras delusion can present in several different contexts. A psychiatric differential diagnosis includes disorders in the schizophrenia spectrum (brief psychotic disorder, schizophreniform disorder, and schizophrenia), schizoaffective disorder, delusional disorder, and substance-induced psychotic disorder. In addition to psychiatric disorders, the Capgras delusion has been shown to occur in several medical conditions, which include stroke, central nervous system tumors, subarachnoid hemorrhage, vitamin B12 deficiency, hepatic encephalopathy, hypothyroidism, hyperparathyroidism, epilepsy, and dementia.^1,2,4,7

A 2007 retrospective study by Josephs examined 47 patients diagnosed with the Capgras delusion from several tertiary care centers. Of those patients, 38 (81%) had a neurodegenerative disease, most commonly Lewy body dementia (LBD).¹ In his review of the Josephs study, Devinsky proposed that the loss of striatal D2 receptors in LBD may be implicated in the manifestation of Capgras delusions.² The data suggest multiple brain regions may be involved, including the frontal lobes, right temporal lobe, right parietal lobe, parahippocampus, and amygdala.^1,2 Most patients in the Josephs study demonstrated global atrophy on imaging studies. One hypothesis is that it is the disconnection of the frontal lobe to other brain regions that may be implicated.^1,2,4 This results in intact recognition of facial features of familiar people, impaired emotional recognition, and impaired self-correction due to executive dysfunction.

Methamphetamine also has been implicated in a small number of cases of Capgras; the proposed mechanism involves dopaminergic neuronal impairment/loss.^1,2 Additionally, Capgras delusions have been described in cases of patients treated with antimalarial medications, such as chloroquine.⁸ Younger patients with the Capgras delusion were more likely to have purely psychiatric comorbidities—such as schizophrenia, substance-induced psychosis, or schizoaffective disorder—as opposed to underlying medical conditions.¹ In the case presented here, the Capgras delusion was thought to be due to a disorder in the schizophrenia spectrum, specifically schizophreniform disorder.

Because an increasing amount of evidence indicates that the Capgras delusion is associated with certain medical conditions, a workup should be performed to rule out underlying medical etiology. Of note, no official guidelines for the workup have been produced for the Capgras delusion. However, the workup may include brain imaging, such as magnetic resonance imaging and/or CT scan to rule out mass lesions, vascular malformations, stroke, or neuro-infectious processes; laboratory tests, such as vitamin B12, liver panel, HIV, rapid plasma reagin, hepatitis B and C viruses, parathyroid hormone levels, urine drug screen, and thyroid panel can be ordered to rule out other medical causes.^1,2,6,7,9

Consultations with internal medicine and neurology departments may be beneficial. Although treatment of the underlying condition may lead to an improvement in the symptoms, full remission in all cases has not been consistently demonstrated in the current literature.^5,7,9,10 Patients with the Capgras delusion are challenging to treat, because their delusions have been shown to be refractory to antipsychotic therapy. However, antipsychotics are currently the mainstay of treatment. Some case studies have shown efficacy with pimozide, tricyclic antidepressants, and mirtazapine.^6,9

One case study in 2014 in India of a 45-year-old woman who believed her husband and son were replaced by imposters out to kill her, showed a 40% to 50% reduction of paranoia, irritability, and suspicious scanning behaviors with a combination of risperidone and trihexyphenidyl. Despite the improvements, the woman continued to have delusions.⁷

A notable feature associated with those experiencing the Capgras delusion is the increased risk of violent behaviors, often because of suspiciousness and paranoia. A 2004 review suggested the risk of violence and homicidality is much higher in male patients compared with that of female patients with the Capgras delusion.⁹ This is despite evidence suggesting that the prevalence of the Capgras delusion seems to be greater in women.^6,9 Moreover, patients often demonstrated social withdrawal and self-isolation prior to violent acts. The victims often were family members or those who live with the patient, which is consistent with the evidence that those most familiar to patients are more likely to be misidentified.^1,2,7,9,10

A 1989 case series that examined 8 cases of the Capgras delusion listed the following violent behaviors: shot and killed father, pointed knife at mother, held knife to mother’s throat, punched parents, threatened to stab husband with scissors, nonspecifically threatened physical harm to family, injured mother with axe, and threatened to stab son with knife and burn him. Seven of the 8 patients lived with the misidentified persons, and 5 of the 8 patients were treatment resistant. The study posited that chronicity of the delusion, content of the delusion, and accessibility of misidentified persons seemed to increase the risk of violent behaviors. These authors went on to suggest that despite the appearance of stability, patients may react violently to minute changes.¹⁰ Overall literature seems to suggest the importance of performing a violence and homicidality assessment with special attention to assessment for themes of hostility toward misidentified individuals.^9,10

Conclusion

The Capgras delusion is an uncommon symptom associated with varied psychiatric, medical, iatrogenic, and neurologic conditions. Treatment of underlying medical conditions may improve or resolve the delusions. However, in this case, the patient did not seem to have any underlying medical conditions, and it was thought that he may have been experiencing a prodrome within the schizophrenia spectrum. This is consistent with the literature, which suggests that those with the delusions at younger ages may have a psychiatric etiology.

Although this patient was responsive to aripiprazole, the Capgras delusion has been known to be resistant to antipsychotic therapy. It is worth considering a medical and neurologic workup with the addition of a psychiatry referral. Further, while the patient in the presented case had the delusion that he had assaulted his mother, whom he misidentified as an imposter, the patient did not demonstrate any hostility and denied thoughts of harming her. However, given the increased risk of violence in patients with the Capgras delusion, a homicidality and violence assessment should be performed. While further recommendations are outside the scope of this article, the provider should be cognizant of local duty-to-warn and duty-to-protect laws regarding potentially homicidal patients.

Many patients admitted to inpatient psychiatric hospitals present with delusions; however, the Capgras delusion is a rare type that often appears as a sequela of certain medical and neurologic conditions.¹ The Capgras delusion is a condition in which a person believes that either an individual or a group of people has been replaced by doubles or imposters.

In 1923, French psychiatrist Joseph Capgras first described the delusion. He and Jean Reboul-Lachaux coauthored a paper on a 53-year-old woman. The patient was a paranoid megalomaniac who “transformed everyone in her entourage, even those closest to her, such as her husband and daughter, into various and numerous doubles.”² She believed she was famous, wealthy, and of royal lineage. Although 3 of her children had died, she believed that they were abducted, and that her only surviving child was replaced by a look-alike.^2,3 Although the prevalence of such delusions in the general population has not been fully studied, a psychiatric hospital in Turkey found a 1.3% prevalence (1.8% women and 0.9% men) in 920 admissions over 5 years.⁴

The Capgras delusion is one of many delusions related to the misidentification of people, places, or objects; these delusions collectively are known as delusional misidentification syndrome (DMS).^5,6 The Fregoli delusion involves the belief that several different people are the same person in disguise. Intermetamorphosis is the belief that an individual has been transformed internally and externally to another person. Subjective doubles is the belief that a doppelganger of the afflicted person exists, living and functioning independently in the world. Reduplicative paramnesia is the belief that a person, place, or object has been duplicated. A rarer example of DMS is the Cotard delusion, which is the belief that the patient himself or herself is dead, putrefying, exsanguinating, or lacking internal organs.

The most common of the DMS is the Capgras delusion. One common presentation of Capgras delusion involves the spouse of the patient, who believes that an imposter of the same sex as their spouse has taken over his or her body. Rarer delusions are those in which a person misidentifies him or herself as the imposter.^3,5,6

Case Presentation

This case involved a 24-year-old male veteran who had received a wide range of mental health diagnoses in the past, including major depressive disorder (MDD) with psychotic features, generalized anxiety disorder, cannabis use disorder, adjustment disorder, and borderline personality disorder. He also had a medical history related to a motor vehicle accident with subsequent intestinal rupture and colostomy placement that had occurred a year and a half prior to presentation. He had no history of brain trauma.

The patient voluntarily presented to the hospital for increased suicidal thoughts and was admitted voluntarily for stabilization and self-harm prevention. He stated that “I feel everything is unreal. I feel suicidal and guilt” and endorsed a plan to either walk into traffic or shoot himself in the head due to increasingly distressing thoughts and memories. According to the patient, he had reported to the police that he raped his ex-girlfriend a year previously, although she denied the claim to the police.

The patient further disclosed that he did not believe his mother was real. “Last year my sister told me it was not 2016, but it was 2022,” he said. “She told me that I have hurt my mother with a padlock—that you could no longer identify her face. I don’t remember having done this. I have lived with her since that time, so I don’t think it’s really [my mother].” He believed that his mother was replaced by “government employees” who were sent to elicit confessions for his behavior while in the military. He expressed guilt over several actions he had performed while in military service, such as punching a wall during boot camp, stealing “soak-up” pads, and napping during work hours. His mother was contacted by a staff psychiatrist in the inpatient unit and denied that any assault had taken place.

The patient’s psychiatric review of systems was positive for visual hallucinations (specifically “blurs” next to his bed in the morning that disappeared as he tried to touch them), depressed mood, anxiety, hopelessness, and insomnia. Pertinent negatives of the review of systems included a denial of manic symptoms and auditory hallucinations. For additional details of his past psychiatric history, the patient admitted that his motor vehicle accident, intestinal rupture, and colostomy were the result of his 1 suicide attempt a year and a half prior after a verbal dispute with the same ex-girlfriend that he believed he had raped. After undergoing extensive medical and surgical treatment, he began seeing an outpatient psychiatrist as well as attending substance use counseling to curtail his marijuana use. He was prescribed a combination of duloxetine and risperidone as an outpatient, which he was taking with intermittent adherence.

Regarding substance use, the patient admitted to using marijuana regularly in the past but quit completely 1 month prior and denied any other drug use or alcohol use. He reported a family history of a sister who was undergoing treatment for bipolar disorder. In his social history, the patient disclosed that he was raised by both parents and described a good childhood with a life absent of abuse in any form. He was single with no children. Although he was unemployed, he lived off the funds from an insurance settlement from his motor vehicle accident. He was living in a trailer with his brother and mother. He also denied having access to firearms.

The patient was overweight, neatly groomed, had good eye contact, and was calm and cooperative. He seemed anxious as evidenced by his continuous shaking of his feet; although speech was normal in rate and tone. He reported his mood as “depressed and anxious” with congruent and tearful affect. His thought process was concrete, although his thought content contained delusions, suicidal ideation, and paranoia. He denied any homicidal thoughts or thoughts of harming others. He did not present with any auditory or visual hallucinations. Insight and judgment were poor. The mental status examination revealed no notable deficits in cognition.

The patient’s differential diagnosis included schizophreniform disorder, exacerbation of MDD with psychotic features, and the psychotic component of cannabis use disorder. His outpatient risperidone and duloxetine were not restarted. Aripiprazole 15 mg daily was prescribed for his delusions, paranoia, and visual hallucinations. The patient also received a prescription for hydroxyzine 50 mg every 6 hours as needed for anxiety.

Because of the nature of his delusions, comorbid medical and neurologic conditions were considered. Neurology consultation recommended a noncontrast head computer tomography (CT) scan and an electroencephalogram (EEG). Laboratory workup included HIV antibody, thyroid panel, chemistry panel, complete blood count, hepatitis B serum antigen, urine drug screen, hepatitis C virus, and rapid plasma reagin. All laboratory results were benign and unremarkable, and the urine drug screen was negative. The noncontrast CT revealed no acute findings, and the EEG revealed no recorded epileptiform abnormalities or seizures.

Throughout his hospital course, the patient remained cooperative with treatment. Three days into the hospitalization, he stated that he believed the entire family had been replaced by imposters. He began to distrust members of his family and was reticent to communicate with them when they attempted to contact him. He also experienced fragmented sleep during his hospital stay, and trazodone 50 mg at bedtime was added.

After aripiprazole was increased to 20 mg daily on hospital day 2 and then to 30 mg daily on hospital day 3 due to the patient’s delusions, he began to doubt the validity of his beliefs. After showing gradual improvement over 6 days, the patient reported that he no longer believed that those memories were real. His sleep, depressed mood, anxiety, and paranoia had markedly improved toward the end of the hospitalization and suicidal ideation/intent resolved. The patient was discharged home to his mother and brother after 6 days of hospitalization with aripiprazole 30 mg daily and trazodone 50 mg at bedtime.

Discussion

The Capgras delusion can present in several different contexts. A psychiatric differential diagnosis includes disorders in the schizophrenia spectrum (brief psychotic disorder, schizophreniform disorder, and schizophrenia), schizoaffective disorder, delusional disorder, and substance-induced psychotic disorder. In addition to psychiatric disorders, the Capgras delusion has been shown to occur in several medical conditions, which include stroke, central nervous system tumors, subarachnoid hemorrhage, vitamin B12 deficiency, hepatic encephalopathy, hypothyroidism, hyperparathyroidism, epilepsy, and dementia.^1,2,4,7

A 2007 retrospective study by Josephs examined 47 patients diagnosed with the Capgras delusion from several tertiary care centers. Of those patients, 38 (81%) had a neurodegenerative disease, most commonly Lewy body dementia (LBD).¹ In his review of the Josephs study, Devinsky proposed that the loss of striatal D2 receptors in LBD may be implicated in the manifestation of Capgras delusions.² The data suggest multiple brain regions may be involved, including the frontal lobes, right temporal lobe, right parietal lobe, parahippocampus, and amygdala.^1,2 Most patients in the Josephs study demonstrated global atrophy on imaging studies. One hypothesis is that it is the disconnection of the frontal lobe to other brain regions that may be implicated.^1,2,4 This results in intact recognition of facial features of familiar people, impaired emotional recognition, and impaired self-correction due to executive dysfunction.

Methamphetamine also has been implicated in a small number of cases of Capgras; the proposed mechanism involves dopaminergic neuronal impairment/loss.^1,2 Additionally, Capgras delusions have been described in cases of patients treated with antimalarial medications, such as chloroquine.⁸ Younger patients with the Capgras delusion were more likely to have purely psychiatric comorbidities—such as schizophrenia, substance-induced psychosis, or schizoaffective disorder—as opposed to underlying medical conditions.¹ In the case presented here, the Capgras delusion was thought to be due to a disorder in the schizophrenia spectrum, specifically schizophreniform disorder.

Because an increasing amount of evidence indicates that the Capgras delusion is associated with certain medical conditions, a workup should be performed to rule out underlying medical etiology. Of note, no official guidelines for the workup have been produced for the Capgras delusion. However, the workup may include brain imaging, such as magnetic resonance imaging and/or CT scan to rule out mass lesions, vascular malformations, stroke, or neuro-infectious processes; laboratory tests, such as vitamin B12, liver panel, HIV, rapid plasma reagin, hepatitis B and C viruses, parathyroid hormone levels, urine drug screen, and thyroid panel can be ordered to rule out other medical causes.^1,2,6,7,9

Consultations with internal medicine and neurology departments may be beneficial. Although treatment of the underlying condition may lead to an improvement in the symptoms, full remission in all cases has not been consistently demonstrated in the current literature.^5,7,9,10 Patients with the Capgras delusion are challenging to treat, because their delusions have been shown to be refractory to antipsychotic therapy. However, antipsychotics are currently the mainstay of treatment. Some case studies have shown efficacy with pimozide, tricyclic antidepressants, and mirtazapine.^6,9

One case study in 2014 in India of a 45-year-old woman who believed her husband and son were replaced by imposters out to kill her, showed a 40% to 50% reduction of paranoia, irritability, and suspicious scanning behaviors with a combination of risperidone and trihexyphenidyl. Despite the improvements, the woman continued to have delusions.⁷

A notable feature associated with those experiencing the Capgras delusion is the increased risk of violent behaviors, often because of suspiciousness and paranoia. A 2004 review suggested the risk of violence and homicidality is much higher in male patients compared with that of female patients with the Capgras delusion.⁹ This is despite evidence suggesting that the prevalence of the Capgras delusion seems to be greater in women.^6,9 Moreover, patients often demonstrated social withdrawal and self-isolation prior to violent acts. The victims often were family members or those who live with the patient, which is consistent with the evidence that those most familiar to patients are more likely to be misidentified.^1,2,7,9,10

A 1989 case series that examined 8 cases of the Capgras delusion listed the following violent behaviors: shot and killed father, pointed knife at mother, held knife to mother’s throat, punched parents, threatened to stab husband with scissors, nonspecifically threatened physical harm to family, injured mother with axe, and threatened to stab son with knife and burn him. Seven of the 8 patients lived with the misidentified persons, and 5 of the 8 patients were treatment resistant. The study posited that chronicity of the delusion, content of the delusion, and accessibility of misidentified persons seemed to increase the risk of violent behaviors. These authors went on to suggest that despite the appearance of stability, patients may react violently to minute changes.¹⁰ Overall literature seems to suggest the importance of performing a violence and homicidality assessment with special attention to assessment for themes of hostility toward misidentified individuals.^9,10

Conclusion

The Capgras delusion is an uncommon symptom associated with varied psychiatric, medical, iatrogenic, and neurologic conditions. Treatment of underlying medical conditions may improve or resolve the delusions. However, in this case, the patient did not seem to have any underlying medical conditions, and it was thought that he may have been experiencing a prodrome within the schizophrenia spectrum. This is consistent with the literature, which suggests that those with the delusions at younger ages may have a psychiatric etiology.

Although this patient was responsive to aripiprazole, the Capgras delusion has been known to be resistant to antipsychotic therapy. It is worth considering a medical and neurologic workup with the addition of a psychiatry referral. Further, while the patient in the presented case had the delusion that he had assaulted his mother, whom he misidentified as an imposter, the patient did not demonstrate any hostility and denied thoughts of harming her. However, given the increased risk of violence in patients with the Capgras delusion, a homicidality and violence assessment should be performed. While further recommendations are outside the scope of this article, the provider should be cognizant of local duty-to-warn and duty-to-protect laws regarding potentially homicidal patients.

John F. Seymour, MBBS, PhD

ATLANTA—The combination of venetoclax and rituximab (VR) should be a standard treatment option for adults with relapsed/refractory chronic lymphocytic leukemia (CLL), according to a speaker at the 2017 ASH Annual Meeting.

Data from the phase 3 MURANO study showed that patients with relapsed/refractory CLL who received VR had significantly longer progression-free survival (PFS) than those who received bendamustine and rituximab (BR).

In addition, “secondary endpoints were consistently in favor of venetoclax-rituximab,” said study investigator John F. Seymour, MBBS, PhD, of Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Adverse events (AEs) were largely consistent with the known safety profiles of the drugs studied, but tumor lysis syndrome (TLS) was infrequent and occurred at a similar frequency in both treatment arms.

“Thus, overall, I believe venetoclax and rituximab should be considered as a suitable standard therapeutic option in patients with relapsed/refractory CLL,” Dr Seymour said.

It is important to note, however, that patients in the VR arm of this study could receive venetoclax for up to 2 years, whereas patients in the BR arm received study treatment for a maximum of six 28-day cycles.

Dr Seymour presented results from MURANO as a late-breaking abstract at ASH (LBA-2). The study was sponsored by Hoffman-La Roche and AbbVie.

MURANO enrolled 389 CLL patients who had received 1 to 3 prior therapies. Patients were randomized to receive VR (n=194) or BR (n=195). Baseline characteristics were similar between the treatment arms.

In both arms, patients received a single monthly dose of rituximab for 6 cycles. The first dose was 375 mg/m², and all subsequent doses were 500 mg/m².

In the VR arm, patients received a 4-week or 5-week dose ramp-up of venetoclax from 20 mg to 400 mg daily. This was intended to mitigate the risk of TLS, which has been observed in previous studies of venetoclax.

Patients in the VR arm continued with daily venetoclax at 400 mg for a maximum of 2 years or until disease progression or cessation due to toxicity. They started receiving rituximab after the ramp-up period (at week 6).

In the BR arm, patients received bendamustine at 70 mg/m² on days 1 and 2 of each 28-day cycle for 6 cycles. Patients could proceed to subsequent therapy if they progressed.

The median follow-up was 23.8 months (range, 0-37.4 months).

Twenty-five percent of patients in the VR arm and 17% in the BR arm discontinued treatment ahead of schedule. Reasons for discontinuation (in the VR and BR arms, respectively) were disease progression (5% and 3%), AEs (12% and 6%), death (1% and 2%), and “other” (6% and 7%).

Survival

The study’s primary endpoint was investigator-assessed PFS. PFS according to an independent review committee (IRC) was a secondary endpoint.

According to investigators, the median PFS was not reached in the VR arm and was 17.0 months in the BR arm (hazard ratio [HR]=0.17, P<0.0001). According to the IRC, the median PFS was not reached in the VR arm and was 18.1 months in the BR arm (HR=0.17, P<0.0001).

According to investigators, the estimated PFS at 24 months was 84.9% in the VR arm and 36.3% in the BR arm. According to the IRC, the 24-month PFS was 82.8% and 37.4%, respectively.

The benefit with VR was consistent across subgroups. Patients had a PFS benefit regardless of their number of prior therapies, deletion 17p status, TP53 mutational status, baseline IGHV mutational status, and whether they had relapsed or refractory disease.

Dr Seymour acknowledged that the differences in treatment duration between the BR and VR arms may have affected the interpretation of these results.

“[T]he treatment duration differed, although, of course, the capacity to deliver more than 6 cycles of bendamustine-rituximab would have been problematic,” he said. “There is some data that antibody treatment may prolong progression-free survival. However, when this study was designed, in 2013, that data was certainly not available. And I believe, currently, maintenance antibody is not an accepted standard of treatment.”

The median overall survival (OS) was not reached in either treatment arm. The 1-year OS rate was 95.9% in the VR arm and 91.1% in the BR arm. The 2-year OS rate was 91.9% and 86.6%, respectively (HR=0.48, P=0.0186).

“[W]ith median follow-up of just on 2 years, there is already a clinically meaningful difference [in OS between the treatment arms],” Dr Seymour said.

“This is not attributable to any difference in availability of novel therapies. Of the 54 patients who received subsequent therapy after progression on the bendamustine-rituximab arm, 40 of those received novel targeted agents.”

Response and MRD

According to investigators, the overall response rate was 93.3% (181/194) in the VR arm and 67.7% (312/195) in the BR arm (P<0.0001). According to the IRC, the overall response rate was 92.3% (179/194) and 72.3% (141/195), respectively (P<0.0001).

According to investigators, the rate of complete response (CR) or CR with incomplete marrow recovery (CRi) was 26.8% (n=52) in the VR arm and 8.2% (n=16) in the BR arm. According to the IRC, the CR/CRi rate was 8.2% (n=16) and 3.6% (n=7), respectively.

Dr Seymour acknowledged the differences in CR/CRi between investigator and IRC assessments. He said 28 of the 42 discrepancies in the VR arm “were attributable to residual CT scan nodal abnormalities in the 16- to 30-mm size.” However, he also noted that 88% of these patients were negative for minimal residual disease (MRD) in the peripheral blood at that time point.

MRD was assessed every 3 months. Patients were counted as MRD-positive if they were positive by either allele-specific oligonucleotide polymerase chain reaction or multicolor flow cytometry. Patients were also counted as MRD-positive if there was a failure to collect a sample.

The proportion of patients who were MRD-negative in the VR and BR arms, respectively, was:

• 45% and 6% at 4 months
• 62% and 13% at 9 months
• 60% and 10% at 12 months
• 57% and 9% at 15 months
• 60% and 5% at 18 months.

Dr Seymour pointed out that 65 patients in the VR arm surpassed the maximum treatment duration for venetoclax (2 years) and therefore stopped receiving the drug, but only 12 of these patients have follow-up beyond 3 months.

“So information about the durability of response after cessation remains immature at the moment,” he said.

Safety

All patients in the VR arm and 98% in the BR arm had at least 1 AE. The rate of serious AEs was 46% and 43%, respectively. The rate of grade 3/4 AEs was 82% and 70%, respectively.

Grade 3/4 AEs with at least a 2% difference in incidence between the treatment arms (in the VR and BR arms, respectively) were neutropenia (58% and 39%), anemia (11% and 14%), thrombocytopenia (6% and 10%), febrile neutropenia (4% and 10%), pneumonia (5% and 8%), infusion-related reactions (2% and 5%), TLS (3% and 1%), hypotension (0% and 3%), hyperglycemia (2% and 0%), and hypogammaglobulinemia (2% and 0%).

The rate of grade 5 AEs was 5% in the VR arm and 6% in the BR arm.

Grade 5 AEs in the VR arm were pneumonia (n=3), sepsis (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1).

Grade 5 AEs in the BR arm included sepsis (n=2), lung cancer (n=2), Listeria sepsis (n=1), Scedosporium infection (n=1), lymphoma (n=1), hemorrhagic stroke (n=1), pulmonary embolism (n=1), acute myeloid leukemia (n=1), and sudden death (n=1).

John F. Seymour, MBBS, PhD

ATLANTA—The combination of venetoclax and rituximab (VR) should be a standard treatment option for adults with relapsed/refractory chronic lymphocytic leukemia (CLL), according to a speaker at the 2017 ASH Annual Meeting.

Data from the phase 3 MURANO study showed that patients with relapsed/refractory CLL who received VR had significantly longer progression-free survival (PFS) than those who received bendamustine and rituximab (BR).

In addition, “secondary endpoints were consistently in favor of venetoclax-rituximab,” said study investigator John F. Seymour, MBBS, PhD, of Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Adverse events (AEs) were largely consistent with the known safety profiles of the drugs studied, but tumor lysis syndrome (TLS) was infrequent and occurred at a similar frequency in both treatment arms.

“Thus, overall, I believe venetoclax and rituximab should be considered as a suitable standard therapeutic option in patients with relapsed/refractory CLL,” Dr Seymour said.

It is important to note, however, that patients in the VR arm of this study could receive venetoclax for up to 2 years, whereas patients in the BR arm received study treatment for a maximum of six 28-day cycles.

Dr Seymour presented results from MURANO as a late-breaking abstract at ASH (LBA-2). The study was sponsored by Hoffman-La Roche and AbbVie.

MURANO enrolled 389 CLL patients who had received 1 to 3 prior therapies. Patients were randomized to receive VR (n=194) or BR (n=195). Baseline characteristics were similar between the treatment arms.

In both arms, patients received a single monthly dose of rituximab for 6 cycles. The first dose was 375 mg/m², and all subsequent doses were 500 mg/m².

In the VR arm, patients received a 4-week or 5-week dose ramp-up of venetoclax from 20 mg to 400 mg daily. This was intended to mitigate the risk of TLS, which has been observed in previous studies of venetoclax.

Patients in the VR arm continued with daily venetoclax at 400 mg for a maximum of 2 years or until disease progression or cessation due to toxicity. They started receiving rituximab after the ramp-up period (at week 6).

In the BR arm, patients received bendamustine at 70 mg/m² on days 1 and 2 of each 28-day cycle for 6 cycles. Patients could proceed to subsequent therapy if they progressed.

The median follow-up was 23.8 months (range, 0-37.4 months).

Twenty-five percent of patients in the VR arm and 17% in the BR arm discontinued treatment ahead of schedule. Reasons for discontinuation (in the VR and BR arms, respectively) were disease progression (5% and 3%), AEs (12% and 6%), death (1% and 2%), and “other” (6% and 7%).

Survival

The study’s primary endpoint was investigator-assessed PFS. PFS according to an independent review committee (IRC) was a secondary endpoint.

According to investigators, the median PFS was not reached in the VR arm and was 17.0 months in the BR arm (hazard ratio [HR]=0.17, P<0.0001). According to the IRC, the median PFS was not reached in the VR arm and was 18.1 months in the BR arm (HR=0.17, P<0.0001).

According to investigators, the estimated PFS at 24 months was 84.9% in the VR arm and 36.3% in the BR arm. According to the IRC, the 24-month PFS was 82.8% and 37.4%, respectively.

The benefit with VR was consistent across subgroups. Patients had a PFS benefit regardless of their number of prior therapies, deletion 17p status, TP53 mutational status, baseline IGHV mutational status, and whether they had relapsed or refractory disease.

Dr Seymour acknowledged that the differences in treatment duration between the BR and VR arms may have affected the interpretation of these results.

“[T]he treatment duration differed, although, of course, the capacity to deliver more than 6 cycles of bendamustine-rituximab would have been problematic,” he said. “There is some data that antibody treatment may prolong progression-free survival. However, when this study was designed, in 2013, that data was certainly not available. And I believe, currently, maintenance antibody is not an accepted standard of treatment.”

The median overall survival (OS) was not reached in either treatment arm. The 1-year OS rate was 95.9% in the VR arm and 91.1% in the BR arm. The 2-year OS rate was 91.9% and 86.6%, respectively (HR=0.48, P=0.0186).

“[W]ith median follow-up of just on 2 years, there is already a clinically meaningful difference [in OS between the treatment arms],” Dr Seymour said.

“This is not attributable to any difference in availability of novel therapies. Of the 54 patients who received subsequent therapy after progression on the bendamustine-rituximab arm, 40 of those received novel targeted agents.”

Response and MRD

According to investigators, the overall response rate was 93.3% (181/194) in the VR arm and 67.7% (312/195) in the BR arm (P<0.0001). According to the IRC, the overall response rate was 92.3% (179/194) and 72.3% (141/195), respectively (P<0.0001).

According to investigators, the rate of complete response (CR) or CR with incomplete marrow recovery (CRi) was 26.8% (n=52) in the VR arm and 8.2% (n=16) in the BR arm. According to the IRC, the CR/CRi rate was 8.2% (n=16) and 3.6% (n=7), respectively.

Dr Seymour acknowledged the differences in CR/CRi between investigator and IRC assessments. He said 28 of the 42 discrepancies in the VR arm “were attributable to residual CT scan nodal abnormalities in the 16- to 30-mm size.” However, he also noted that 88% of these patients were negative for minimal residual disease (MRD) in the peripheral blood at that time point.

MRD was assessed every 3 months. Patients were counted as MRD-positive if they were positive by either allele-specific oligonucleotide polymerase chain reaction or multicolor flow cytometry. Patients were also counted as MRD-positive if there was a failure to collect a sample.

The proportion of patients who were MRD-negative in the VR and BR arms, respectively, was:

• 45% and 6% at 4 months
• 62% and 13% at 9 months
• 60% and 10% at 12 months
• 57% and 9% at 15 months
• 60% and 5% at 18 months.

Dr Seymour pointed out that 65 patients in the VR arm surpassed the maximum treatment duration for venetoclax (2 years) and therefore stopped receiving the drug, but only 12 of these patients have follow-up beyond 3 months.

“So information about the durability of response after cessation remains immature at the moment,” he said.

Safety

All patients in the VR arm and 98% in the BR arm had at least 1 AE. The rate of serious AEs was 46% and 43%, respectively. The rate of grade 3/4 AEs was 82% and 70%, respectively.

Grade 3/4 AEs with at least a 2% difference in incidence between the treatment arms (in the VR and BR arms, respectively) were neutropenia (58% and 39%), anemia (11% and 14%), thrombocytopenia (6% and 10%), febrile neutropenia (4% and 10%), pneumonia (5% and 8%), infusion-related reactions (2% and 5%), TLS (3% and 1%), hypotension (0% and 3%), hyperglycemia (2% and 0%), and hypogammaglobulinemia (2% and 0%).

The rate of grade 5 AEs was 5% in the VR arm and 6% in the BR arm.

Grade 5 AEs in the VR arm were pneumonia (n=3), sepsis (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1).

Grade 5 AEs in the BR arm included sepsis (n=2), lung cancer (n=2), Listeria sepsis (n=1), Scedosporium infection (n=1), lymphoma (n=1), hemorrhagic stroke (n=1), pulmonary embolism (n=1), acute myeloid leukemia (n=1), and sudden death (n=1).

John F. Seymour, MBBS, PhD

ATLANTA—The combination of venetoclax and rituximab (VR) should be a standard treatment option for adults with relapsed/refractory chronic lymphocytic leukemia (CLL), according to a speaker at the 2017 ASH Annual Meeting.

Data from the phase 3 MURANO study showed that patients with relapsed/refractory CLL who received VR had significantly longer progression-free survival (PFS) than those who received bendamustine and rituximab (BR).

In addition, “secondary endpoints were consistently in favor of venetoclax-rituximab,” said study investigator John F. Seymour, MBBS, PhD, of Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Adverse events (AEs) were largely consistent with the known safety profiles of the drugs studied, but tumor lysis syndrome (TLS) was infrequent and occurred at a similar frequency in both treatment arms.

“Thus, overall, I believe venetoclax and rituximab should be considered as a suitable standard therapeutic option in patients with relapsed/refractory CLL,” Dr Seymour said.

It is important to note, however, that patients in the VR arm of this study could receive venetoclax for up to 2 years, whereas patients in the BR arm received study treatment for a maximum of six 28-day cycles.

Dr Seymour presented results from MURANO as a late-breaking abstract at ASH (LBA-2). The study was sponsored by Hoffman-La Roche and AbbVie.

MURANO enrolled 389 CLL patients who had received 1 to 3 prior therapies. Patients were randomized to receive VR (n=194) or BR (n=195). Baseline characteristics were similar between the treatment arms.

In both arms, patients received a single monthly dose of rituximab for 6 cycles. The first dose was 375 mg/m², and all subsequent doses were 500 mg/m².

In the VR arm, patients received a 4-week or 5-week dose ramp-up of venetoclax from 20 mg to 400 mg daily. This was intended to mitigate the risk of TLS, which has been observed in previous studies of venetoclax.

Patients in the VR arm continued with daily venetoclax at 400 mg for a maximum of 2 years or until disease progression or cessation due to toxicity. They started receiving rituximab after the ramp-up period (at week 6).

In the BR arm, patients received bendamustine at 70 mg/m² on days 1 and 2 of each 28-day cycle for 6 cycles. Patients could proceed to subsequent therapy if they progressed.

The median follow-up was 23.8 months (range, 0-37.4 months).

Twenty-five percent of patients in the VR arm and 17% in the BR arm discontinued treatment ahead of schedule. Reasons for discontinuation (in the VR and BR arms, respectively) were disease progression (5% and 3%), AEs (12% and 6%), death (1% and 2%), and “other” (6% and 7%).

Survival

The study’s primary endpoint was investigator-assessed PFS. PFS according to an independent review committee (IRC) was a secondary endpoint.

According to investigators, the median PFS was not reached in the VR arm and was 17.0 months in the BR arm (hazard ratio [HR]=0.17, P<0.0001). According to the IRC, the median PFS was not reached in the VR arm and was 18.1 months in the BR arm (HR=0.17, P<0.0001).

According to investigators, the estimated PFS at 24 months was 84.9% in the VR arm and 36.3% in the BR arm. According to the IRC, the 24-month PFS was 82.8% and 37.4%, respectively.

The benefit with VR was consistent across subgroups. Patients had a PFS benefit regardless of their number of prior therapies, deletion 17p status, TP53 mutational status, baseline IGHV mutational status, and whether they had relapsed or refractory disease.

Dr Seymour acknowledged that the differences in treatment duration between the BR and VR arms may have affected the interpretation of these results.

“[T]he treatment duration differed, although, of course, the capacity to deliver more than 6 cycles of bendamustine-rituximab would have been problematic,” he said. “There is some data that antibody treatment may prolong progression-free survival. However, when this study was designed, in 2013, that data was certainly not available. And I believe, currently, maintenance antibody is not an accepted standard of treatment.”

The median overall survival (OS) was not reached in either treatment arm. The 1-year OS rate was 95.9% in the VR arm and 91.1% in the BR arm. The 2-year OS rate was 91.9% and 86.6%, respectively (HR=0.48, P=0.0186).

“[W]ith median follow-up of just on 2 years, there is already a clinically meaningful difference [in OS between the treatment arms],” Dr Seymour said.

“This is not attributable to any difference in availability of novel therapies. Of the 54 patients who received subsequent therapy after progression on the bendamustine-rituximab arm, 40 of those received novel targeted agents.”

Response and MRD

According to investigators, the overall response rate was 93.3% (181/194) in the VR arm and 67.7% (312/195) in the BR arm (P<0.0001). According to the IRC, the overall response rate was 92.3% (179/194) and 72.3% (141/195), respectively (P<0.0001).

According to investigators, the rate of complete response (CR) or CR with incomplete marrow recovery (CRi) was 26.8% (n=52) in the VR arm and 8.2% (n=16) in the BR arm. According to the IRC, the CR/CRi rate was 8.2% (n=16) and 3.6% (n=7), respectively.

Dr Seymour acknowledged the differences in CR/CRi between investigator and IRC assessments. He said 28 of the 42 discrepancies in the VR arm “were attributable to residual CT scan nodal abnormalities in the 16- to 30-mm size.” However, he also noted that 88% of these patients were negative for minimal residual disease (MRD) in the peripheral blood at that time point.

MRD was assessed every 3 months. Patients were counted as MRD-positive if they were positive by either allele-specific oligonucleotide polymerase chain reaction or multicolor flow cytometry. Patients were also counted as MRD-positive if there was a failure to collect a sample.

The proportion of patients who were MRD-negative in the VR and BR arms, respectively, was:

• 45% and 6% at 4 months
• 62% and 13% at 9 months
• 60% and 10% at 12 months
• 57% and 9% at 15 months
• 60% and 5% at 18 months.

Dr Seymour pointed out that 65 patients in the VR arm surpassed the maximum treatment duration for venetoclax (2 years) and therefore stopped receiving the drug, but only 12 of these patients have follow-up beyond 3 months.

“So information about the durability of response after cessation remains immature at the moment,” he said.

Safety

All patients in the VR arm and 98% in the BR arm had at least 1 AE. The rate of serious AEs was 46% and 43%, respectively. The rate of grade 3/4 AEs was 82% and 70%, respectively.

Grade 3/4 AEs with at least a 2% difference in incidence between the treatment arms (in the VR and BR arms, respectively) were neutropenia (58% and 39%), anemia (11% and 14%), thrombocytopenia (6% and 10%), febrile neutropenia (4% and 10%), pneumonia (5% and 8%), infusion-related reactions (2% and 5%), TLS (3% and 1%), hypotension (0% and 3%), hyperglycemia (2% and 0%), and hypogammaglobulinemia (2% and 0%).

The rate of grade 5 AEs was 5% in the VR arm and 6% in the BR arm.

Grade 5 AEs in the VR arm were pneumonia (n=3), sepsis (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1).

Grade 5 AEs in the BR arm included sepsis (n=2), lung cancer (n=2), Listeria sepsis (n=1), Scedosporium infection (n=1), lymphoma (n=1), hemorrhagic stroke (n=1), pulmonary embolism (n=1), acute myeloid leukemia (n=1), and sudden death (n=1).

If you provide better Medicaid payment, pediatricians will participate.

“Office-based primary care pediatricians, who had historically been more resistant to [Medicaid] participation than either their subspecialist or safety net and institution-based peers, increased their participation in the Medicaid program nationally from before to after the 2013 to 2014 Medicaid payment increase,” noted Suk-fong S. Tang, PhD, research analyst at American Academy of Pediatrics, and colleagues.

“That we found participation increases in 4 of 5 indicators nationally and by different measures in the majority of studied states speaks to the robustness of our conclusions,” they wrote.

The researchers looked at office-based primary care pediatricians’ participation in Medicaid between 2011 to 2012 and 2015 to 2016 (prior to and following the temporary Medicaid pay increases provided by the Affordable Care Act) across 27 states and found that those accepting at least some new patients insured by Medicaid increased by 3% to 77%. Pediatricians accepting all new patients insured by Medicaid increased by 6% to 43% and those accepting these patients at least as often as new privately insured patients increased by 6% to 56%. The average percentage of patients insured by Medicaid per provider panel increased by 6% to 31%.

copyright Kativ/iStockphoto.com

[email protected]

SOURCE: Tang S et al. Pediatrics 2018 Jan. doi: 10.1542/peds.2017-2570.

If you provide better Medicaid payment, pediatricians will participate.

“Office-based primary care pediatricians, who had historically been more resistant to [Medicaid] participation than either their subspecialist or safety net and institution-based peers, increased their participation in the Medicaid program nationally from before to after the 2013 to 2014 Medicaid payment increase,” noted Suk-fong S. Tang, PhD, research analyst at American Academy of Pediatrics, and colleagues.

“That we found participation increases in 4 of 5 indicators nationally and by different measures in the majority of studied states speaks to the robustness of our conclusions,” they wrote.

The researchers looked at office-based primary care pediatricians’ participation in Medicaid between 2011 to 2012 and 2015 to 2016 (prior to and following the temporary Medicaid pay increases provided by the Affordable Care Act) across 27 states and found that those accepting at least some new patients insured by Medicaid increased by 3% to 77%. Pediatricians accepting all new patients insured by Medicaid increased by 6% to 43% and those accepting these patients at least as often as new privately insured patients increased by 6% to 56%. The average percentage of patients insured by Medicaid per provider panel increased by 6% to 31%.

copyright Kativ/iStockphoto.com

[email protected]

SOURCE: Tang S et al. Pediatrics 2018 Jan. doi: 10.1542/peds.2017-2570.

If you provide better Medicaid payment, pediatricians will participate.

“Office-based primary care pediatricians, who had historically been more resistant to [Medicaid] participation than either their subspecialist or safety net and institution-based peers, increased their participation in the Medicaid program nationally from before to after the 2013 to 2014 Medicaid payment increase,” noted Suk-fong S. Tang, PhD, research analyst at American Academy of Pediatrics, and colleagues.

“That we found participation increases in 4 of 5 indicators nationally and by different measures in the majority of studied states speaks to the robustness of our conclusions,” they wrote.

The researchers looked at office-based primary care pediatricians’ participation in Medicaid between 2011 to 2012 and 2015 to 2016 (prior to and following the temporary Medicaid pay increases provided by the Affordable Care Act) across 27 states and found that those accepting at least some new patients insured by Medicaid increased by 3% to 77%. Pediatricians accepting all new patients insured by Medicaid increased by 6% to 43% and those accepting these patients at least as often as new privately insured patients increased by 6% to 56%. The average percentage of patients insured by Medicaid per provider panel increased by 6% to 31%.

copyright Kativ/iStockphoto.com

[email protected]

SOURCE: Tang S et al. Pediatrics 2018 Jan. doi: 10.1542/peds.2017-2570.

The Food and Drug Administration has approved ertugliflozin for use both as monotherapy and in combination with sitagliptin or metformin to control blood glucose in patients with type 2 diabetes.

The FDA approval covers ertugliflozin monotherapy (Steglatro, Merck and Pfizer) and ertugliflozin plus sitagliptin, a dipeptidyl peptidase–4 (DPP-4) inhibitor, as a fixed-dose combination (Steglujan, Merck) and ertugliflozin plus metformin (Segluromet, Merck).

Ertugliflozin is the third sodium glucose cotransporter 2 (SGLT2) inhibitor to win FDA approval. Another such agent, empagliflozin, recently won a second indication for lowering the risk for cardiovascular death in adults with type 2 diabetes and established heart disease.

The American Diabetes Association recognized the value of SGLT2 inhibitors in patients with type 2 diabetes in its 2018 Standards of Care in Diabetes, now recommending that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the SGLT2 inhibitor empagliflozin or the glucagonlike peptide–1 agonist liraglutide – to the regimens of patients with diabetes and atherosclerotic cardiovascular disease (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).

[email protected]

The Food and Drug Administration has approved ertugliflozin for use both as monotherapy and in combination with sitagliptin or metformin to control blood glucose in patients with type 2 diabetes.

The FDA approval covers ertugliflozin monotherapy (Steglatro, Merck and Pfizer) and ertugliflozin plus sitagliptin, a dipeptidyl peptidase–4 (DPP-4) inhibitor, as a fixed-dose combination (Steglujan, Merck) and ertugliflozin plus metformin (Segluromet, Merck).

Ertugliflozin is the third sodium glucose cotransporter 2 (SGLT2) inhibitor to win FDA approval. Another such agent, empagliflozin, recently won a second indication for lowering the risk for cardiovascular death in adults with type 2 diabetes and established heart disease.

The American Diabetes Association recognized the value of SGLT2 inhibitors in patients with type 2 diabetes in its 2018 Standards of Care in Diabetes, now recommending that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the SGLT2 inhibitor empagliflozin or the glucagonlike peptide–1 agonist liraglutide – to the regimens of patients with diabetes and atherosclerotic cardiovascular disease (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).

[email protected]

The Food and Drug Administration has approved ertugliflozin for use both as monotherapy and in combination with sitagliptin or metformin to control blood glucose in patients with type 2 diabetes.

The FDA approval covers ertugliflozin monotherapy (Steglatro, Merck and Pfizer) and ertugliflozin plus sitagliptin, a dipeptidyl peptidase–4 (DPP-4) inhibitor, as a fixed-dose combination (Steglujan, Merck) and ertugliflozin plus metformin (Segluromet, Merck).

Ertugliflozin is the third sodium glucose cotransporter 2 (SGLT2) inhibitor to win FDA approval. Another such agent, empagliflozin, recently won a second indication for lowering the risk for cardiovascular death in adults with type 2 diabetes and established heart disease.

The American Diabetes Association recognized the value of SGLT2 inhibitors in patients with type 2 diabetes in its 2018 Standards of Care in Diabetes, now recommending that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the SGLT2 inhibitor empagliflozin or the glucagonlike peptide–1 agonist liraglutide – to the regimens of patients with diabetes and atherosclerotic cardiovascular disease (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).

[email protected]

MONTREAL – Loneliness is associated with poorer health, but isn’t necessarily more common among older adults; one in five adults in a primary care population reported being lonely, a number higher than previously reported, a study showed.

In a survey of 940 adults seeking care in primary care clinics, 193 (21%) reported loneliness, with women more likely than men to say they were lonely. “Respondents identifying as having poorer health classifications were more likely to report high loneliness scores,” said Rebecca Mullen, MD, and her colleagues in a poster presented at the annual meeting of the North American Primary Care Research Group.

Those who said they were lonely also had a higher level of health care utilization, and reported they had a lower number of healthy days than the respondents who didn’t report loneliness.

Kari Oakes/Frontline Medical News

The study was conducted in outpatient practice-based research networks in both urban and rural settings in the states of Virginia and Colorado. Participants were adult, English-speaking primary care patients who were given the UCLA Three-Item Loneliness Scale. The scale asks how often respondents feel a lack of companionship, feel left out, and feel isolated from others; responses are “hardly ever,” “sometimes,” and “often.”

The investigators sought to determine whether high loneliness scores on this scale – the primary outcome – were correlated with health care utilization, the number of healthy days reported by patients, and demographic information. These associations were the study’s secondary outcomes.

After statistical analysis, several variables emerged as being significantly associated with high loneliness scores. These included the number of reported days with poor physical or mental health (odds ratio, 1.06), the number of primary care office visits (OR, 1.06), the number of hospitalizations (OR, 1.16), the number of emergency department or urgent care visits (OR ,1.27), and gender.

When compared with male respondents, females had an OR of 1.56 for reporting loneliness.

Race and ethnicity were not associated with a greater risk of loneliness; neither were disability or employment status, or whether the respondent was in a relationship.

And despite other studies indicating an increased prevalence of loneliness among the elderly, “our findings suggest loneliness is not age related,” wrote Dr. Mullen and her colleagues.

The investigators said they plan to examine their data further, to see if factors such as living in a rural or urban environment are associated with differences in loneliness. Going into still more detail, they plan to use demographic data to plot out respondents’ residences, and then look for spatial associations and links to other comorbidities. Integrating the questionnaire with data from the electronic record will allow Dr. Mullen and her colleagues to search for further associations as well, they said.

Finally, the investigators plan to build partnerships with the community, public health agencies, and those involved in health policy to build interventions against loneliness targeted at both the individual and the community. Some of these interventions, they said, could begin in the clinic: “[T]he primary care health care setting may be an appropriate context to consider intervention delivery.”

Dr. Mullen reported no relevant financial conflicts of interest.

[email protected]

SOURCE: Mullen R et al. Abstract P196.

MONTREAL – Loneliness is associated with poorer health, but isn’t necessarily more common among older adults; one in five adults in a primary care population reported being lonely, a number higher than previously reported, a study showed.

In a survey of 940 adults seeking care in primary care clinics, 193 (21%) reported loneliness, with women more likely than men to say they were lonely. “Respondents identifying as having poorer health classifications were more likely to report high loneliness scores,” said Rebecca Mullen, MD, and her colleagues in a poster presented at the annual meeting of the North American Primary Care Research Group.

Those who said they were lonely also had a higher level of health care utilization, and reported they had a lower number of healthy days than the respondents who didn’t report loneliness.

Kari Oakes/Frontline Medical News

The study was conducted in outpatient practice-based research networks in both urban and rural settings in the states of Virginia and Colorado. Participants were adult, English-speaking primary care patients who were given the UCLA Three-Item Loneliness Scale. The scale asks how often respondents feel a lack of companionship, feel left out, and feel isolated from others; responses are “hardly ever,” “sometimes,” and “often.”

The investigators sought to determine whether high loneliness scores on this scale – the primary outcome – were correlated with health care utilization, the number of healthy days reported by patients, and demographic information. These associations were the study’s secondary outcomes.

After statistical analysis, several variables emerged as being significantly associated with high loneliness scores. These included the number of reported days with poor physical or mental health (odds ratio, 1.06), the number of primary care office visits (OR, 1.06), the number of hospitalizations (OR, 1.16), the number of emergency department or urgent care visits (OR ,1.27), and gender.

When compared with male respondents, females had an OR of 1.56 for reporting loneliness.

Race and ethnicity were not associated with a greater risk of loneliness; neither were disability or employment status, or whether the respondent was in a relationship.

And despite other studies indicating an increased prevalence of loneliness among the elderly, “our findings suggest loneliness is not age related,” wrote Dr. Mullen and her colleagues.

The investigators said they plan to examine their data further, to see if factors such as living in a rural or urban environment are associated with differences in loneliness. Going into still more detail, they plan to use demographic data to plot out respondents’ residences, and then look for spatial associations and links to other comorbidities. Integrating the questionnaire with data from the electronic record will allow Dr. Mullen and her colleagues to search for further associations as well, they said.

Finally, the investigators plan to build partnerships with the community, public health agencies, and those involved in health policy to build interventions against loneliness targeted at both the individual and the community. Some of these interventions, they said, could begin in the clinic: “[T]he primary care health care setting may be an appropriate context to consider intervention delivery.”

Dr. Mullen reported no relevant financial conflicts of interest.

[email protected]

SOURCE: Mullen R et al. Abstract P196.

MONTREAL – Loneliness is associated with poorer health, but isn’t necessarily more common among older adults; one in five adults in a primary care population reported being lonely, a number higher than previously reported, a study showed.

In a survey of 940 adults seeking care in primary care clinics, 193 (21%) reported loneliness, with women more likely than men to say they were lonely. “Respondents identifying as having poorer health classifications were more likely to report high loneliness scores,” said Rebecca Mullen, MD, and her colleagues in a poster presented at the annual meeting of the North American Primary Care Research Group.

Those who said they were lonely also had a higher level of health care utilization, and reported they had a lower number of healthy days than the respondents who didn’t report loneliness.

Kari Oakes/Frontline Medical News

The study was conducted in outpatient practice-based research networks in both urban and rural settings in the states of Virginia and Colorado. Participants were adult, English-speaking primary care patients who were given the UCLA Three-Item Loneliness Scale. The scale asks how often respondents feel a lack of companionship, feel left out, and feel isolated from others; responses are “hardly ever,” “sometimes,” and “often.”

The investigators sought to determine whether high loneliness scores on this scale – the primary outcome – were correlated with health care utilization, the number of healthy days reported by patients, and demographic information. These associations were the study’s secondary outcomes.

After statistical analysis, several variables emerged as being significantly associated with high loneliness scores. These included the number of reported days with poor physical or mental health (odds ratio, 1.06), the number of primary care office visits (OR, 1.06), the number of hospitalizations (OR, 1.16), the number of emergency department or urgent care visits (OR ,1.27), and gender.

When compared with male respondents, females had an OR of 1.56 for reporting loneliness.

Race and ethnicity were not associated with a greater risk of loneliness; neither were disability or employment status, or whether the respondent was in a relationship.

And despite other studies indicating an increased prevalence of loneliness among the elderly, “our findings suggest loneliness is not age related,” wrote Dr. Mullen and her colleagues.

The investigators said they plan to examine their data further, to see if factors such as living in a rural or urban environment are associated with differences in loneliness. Going into still more detail, they plan to use demographic data to plot out respondents’ residences, and then look for spatial associations and links to other comorbidities. Integrating the questionnaire with data from the electronic record will allow Dr. Mullen and her colleagues to search for further associations as well, they said.

Finally, the investigators plan to build partnerships with the community, public health agencies, and those involved in health policy to build interventions against loneliness targeted at both the individual and the community. Some of these interventions, they said, could begin in the clinic: “[T]he primary care health care setting may be an appropriate context to consider intervention delivery.”

Dr. Mullen reported no relevant financial conflicts of interest.

[email protected]

SOURCE: Mullen R et al. Abstract P196.

Clinical question: Is urgent endoscopy (less than 6 hours after ED presentation) better than elective endoscopy (6-48 hours after presentation) to decrease mortality and rebleeding in high-risk patients with acute nonvariceal upper GI bleeding (ANVGIB)?

Background: High-risk ANVGIB patients (Glasgow-Blatchford score greater than 7) are recommended to undergo early endoscopy, within 24 hours of presentation. The impact of urgent endoscopy (less than 6 hours) on patient outcomes is not clear.

Study design: Retrospective observation study.

Setting: Single tertiary referral center in South Korea.

Synopsis: Investigators retrospectively reviewed 961 high-risk ANVGIB patients, 571 patients underwent urgent endoscopy and 390 patients had elective endoscopy (6-48 hours), to compare clinical features and outcomes. The urgent group was slightly older, had a higher Rockall score, lower blood pressure, and higher incidence of shock on admission.
Urgent endoscopy was associated with significantly lower 28-day mortality (1.6% vs 3.8%). Urgent endoscopy also was associated with higher packed red blood cell transfusion volume (2.6 U vs. 2.3 U) and greater need for endoscopic intervention (69.5% vs. 53.5%) and embolization (2.8% vs. 0.5%). There was no significant difference in rebleeding rates, need for ICU admission, vasopressor use, and length of hospital stay between the urgent and elective endoscopy groups. The authors conclude that urgent endoscopy was associated with lower mortality rate but not rebleeding in high-risk patients with ANVGIB.
Despite differences between these two groups, based on this retrospective data, it is reasonable to suggest that urgent endoscopy may be beneficial for reducing mortality in high-risk patients with ANVGIB.

Bottom line: Urgent endoscopy may be beneficial in reducing mortality in high-risk patients with acute nonvariceal gastrointestinal bleeding.

Citation: Cho SH et al. Outcomes and role of urgent endoscopy in high-risk patients with acute nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2017 Jun 19. pii: S1542-3565(17)30736-X.

Dr. Patel is a hospitalist and an assistant professor of medicine, Duke University Health System.

Clinical question: Is urgent endoscopy (less than 6 hours after ED presentation) better than elective endoscopy (6-48 hours after presentation) to decrease mortality and rebleeding in high-risk patients with acute nonvariceal upper GI bleeding (ANVGIB)?

Background: High-risk ANVGIB patients (Glasgow-Blatchford score greater than 7) are recommended to undergo early endoscopy, within 24 hours of presentation. The impact of urgent endoscopy (less than 6 hours) on patient outcomes is not clear.

Study design: Retrospective observation study.

Setting: Single tertiary referral center in South Korea.

Synopsis: Investigators retrospectively reviewed 961 high-risk ANVGIB patients, 571 patients underwent urgent endoscopy and 390 patients had elective endoscopy (6-48 hours), to compare clinical features and outcomes. The urgent group was slightly older, had a higher Rockall score, lower blood pressure, and higher incidence of shock on admission.
Urgent endoscopy was associated with significantly lower 28-day mortality (1.6% vs 3.8%). Urgent endoscopy also was associated with higher packed red blood cell transfusion volume (2.6 U vs. 2.3 U) and greater need for endoscopic intervention (69.5% vs. 53.5%) and embolization (2.8% vs. 0.5%). There was no significant difference in rebleeding rates, need for ICU admission, vasopressor use, and length of hospital stay between the urgent and elective endoscopy groups. The authors conclude that urgent endoscopy was associated with lower mortality rate but not rebleeding in high-risk patients with ANVGIB.
Despite differences between these two groups, based on this retrospective data, it is reasonable to suggest that urgent endoscopy may be beneficial for reducing mortality in high-risk patients with ANVGIB.

Bottom line: Urgent endoscopy may be beneficial in reducing mortality in high-risk patients with acute nonvariceal gastrointestinal bleeding.

Citation: Cho SH et al. Outcomes and role of urgent endoscopy in high-risk patients with acute nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2017 Jun 19. pii: S1542-3565(17)30736-X.

Dr. Patel is a hospitalist and an assistant professor of medicine, Duke University Health System.

Clinical question: Is urgent endoscopy (less than 6 hours after ED presentation) better than elective endoscopy (6-48 hours after presentation) to decrease mortality and rebleeding in high-risk patients with acute nonvariceal upper GI bleeding (ANVGIB)?

Background: High-risk ANVGIB patients (Glasgow-Blatchford score greater than 7) are recommended to undergo early endoscopy, within 24 hours of presentation. The impact of urgent endoscopy (less than 6 hours) on patient outcomes is not clear.

Study design: Retrospective observation study.

Setting: Single tertiary referral center in South Korea.

Synopsis: Investigators retrospectively reviewed 961 high-risk ANVGIB patients, 571 patients underwent urgent endoscopy and 390 patients had elective endoscopy (6-48 hours), to compare clinical features and outcomes. The urgent group was slightly older, had a higher Rockall score, lower blood pressure, and higher incidence of shock on admission.
Urgent endoscopy was associated with significantly lower 28-day mortality (1.6% vs 3.8%). Urgent endoscopy also was associated with higher packed red blood cell transfusion volume (2.6 U vs. 2.3 U) and greater need for endoscopic intervention (69.5% vs. 53.5%) and embolization (2.8% vs. 0.5%). There was no significant difference in rebleeding rates, need for ICU admission, vasopressor use, and length of hospital stay between the urgent and elective endoscopy groups. The authors conclude that urgent endoscopy was associated with lower mortality rate but not rebleeding in high-risk patients with ANVGIB.
Despite differences between these two groups, based on this retrospective data, it is reasonable to suggest that urgent endoscopy may be beneficial for reducing mortality in high-risk patients with ANVGIB.

Bottom line: Urgent endoscopy may be beneficial in reducing mortality in high-risk patients with acute nonvariceal gastrointestinal bleeding.

Citation: Cho SH et al. Outcomes and role of urgent endoscopy in high-risk patients with acute nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2017 Jun 19. pii: S1542-3565(17)30736-X.

Dr. Patel is a hospitalist and an assistant professor of medicine, Duke University Health System.

BACKGROUND: Identifying hospitals that are both early and consistent adopters of high-value care can help shed light on the culture and practices at those institutions that are necessary to promote high-value care nationwide. The use of troponin testing to diagnose acute myocardial infarction (AMI), and not testing for myoglobin or creatine kinase-MB (CK-MB), is a high-value recommendation of the Choosing Wisely® campaign.

OBJECTIVE: To examine the variation in cardiac biomarker testing and the effect of the Choosing Wisely® troponin-only testing recommendation for the diagnosis of AMI.

DESIGN: A retrospective, observational study using administrative ordering data from Vizient’s Clinical Database/Resource Manager.

PATIENTS: Hospitalized patients with a principal discharge diagnosis of AMI.

INTERVENTION: The Choosing Wisely® recommendation to order troponin-only testing to diagnose AMI was released during the first quarter of 2015.

RESULTS: In 19 hospitals, troponin-only testing was consistently ordered to diagnose AMI before the Choosing Wisely® recommendation and throughout the study period. In 34 hospitals, both troponin testing and myoglobin/CK-MB testing were ordered to diagnose AMI even after the Choosing Wisely® recommendation. In 26 hospitals with low rates of troponin-only testing before the Choosing Wisely® recommendation, the release of the recommendation was associated with a statistically significant increase in the rate of troponin-only testing to diagnose AMI.

CONCLUSION: In institutions with low rates of troponin-only testing prior to the Choosing Wisely® recommendation, the recommendation was associated with a significant increase in the rate of troponin-only testing.

Read the entire article in the Dec. 2017 issue of the Journal of Hospital Medicine.

Also in JHM this month

Hospital perceptions of Medicare’s Sepsis Quality Reporting Initiative

AUTHORS: Ian J. Barbash, MD, MS; Kimberly J. Rak, PhD; Courtney C. Kuza, MPH; and Jeremy M. Kahn, MD, MS

Health literacy and hospital length of stay: An inpatient cohort study

AUTHORS: Ethan G. Jaffee, MD; Vineet M. Arora, MD, MAPP; Madeleine I. Matthiesen, MD; David O. Meltzer, MD, PhD, MHM; and Valerie G. Press, MD, FAAP, FACP, MPH

How exemplary teaching physicians interact with hospitalized patients

AUTHORS: Sanjay Saint, MD, MPH, FHM; Molly Harrod, PhD; Karen E. Fowler, MPH; and Nathan Houchens, MD, FACP, FHM

A randomized cohort controlled trial to compare intern sign-out training interventions

AUTHORS: Soo-Hoon Lee, PhD; Christopher Terndrup, MD; Phillip H. Phan, PhD; Sandra E. Zaeh, MD; Kwame Atsina, MD; Nicole Minkove, MD; Alexander Billioux, MD; DPhil, Souvik Chatterjee, MD; Idoreyin Montague, MD; Bennett Clark, MD; Andrew Hughes, MD; and Sanjay V. Desai, MD

BACKGROUND: Identifying hospitals that are both early and consistent adopters of high-value care can help shed light on the culture and practices at those institutions that are necessary to promote high-value care nationwide. The use of troponin testing to diagnose acute myocardial infarction (AMI), and not testing for myoglobin or creatine kinase-MB (CK-MB), is a high-value recommendation of the Choosing Wisely® campaign.

OBJECTIVE: To examine the variation in cardiac biomarker testing and the effect of the Choosing Wisely® troponin-only testing recommendation for the diagnosis of AMI.

DESIGN: A retrospective, observational study using administrative ordering data from Vizient’s Clinical Database/Resource Manager.

PATIENTS: Hospitalized patients with a principal discharge diagnosis of AMI.

INTERVENTION: The Choosing Wisely® recommendation to order troponin-only testing to diagnose AMI was released during the first quarter of 2015.

RESULTS: In 19 hospitals, troponin-only testing was consistently ordered to diagnose AMI before the Choosing Wisely® recommendation and throughout the study period. In 34 hospitals, both troponin testing and myoglobin/CK-MB testing were ordered to diagnose AMI even after the Choosing Wisely® recommendation. In 26 hospitals with low rates of troponin-only testing before the Choosing Wisely® recommendation, the release of the recommendation was associated with a statistically significant increase in the rate of troponin-only testing to diagnose AMI.

CONCLUSION: In institutions with low rates of troponin-only testing prior to the Choosing Wisely® recommendation, the recommendation was associated with a significant increase in the rate of troponin-only testing.

Read the entire article in the Dec. 2017 issue of the Journal of Hospital Medicine.

Also in JHM this month

Hospital perceptions of Medicare’s Sepsis Quality Reporting Initiative

AUTHORS: Ian J. Barbash, MD, MS; Kimberly J. Rak, PhD; Courtney C. Kuza, MPH; and Jeremy M. Kahn, MD, MS

Health literacy and hospital length of stay: An inpatient cohort study

AUTHORS: Ethan G. Jaffee, MD; Vineet M. Arora, MD, MAPP; Madeleine I. Matthiesen, MD; David O. Meltzer, MD, PhD, MHM; and Valerie G. Press, MD, FAAP, FACP, MPH

How exemplary teaching physicians interact with hospitalized patients

AUTHORS: Sanjay Saint, MD, MPH, FHM; Molly Harrod, PhD; Karen E. Fowler, MPH; and Nathan Houchens, MD, FACP, FHM

A randomized cohort controlled trial to compare intern sign-out training interventions

AUTHORS: Soo-Hoon Lee, PhD; Christopher Terndrup, MD; Phillip H. Phan, PhD; Sandra E. Zaeh, MD; Kwame Atsina, MD; Nicole Minkove, MD; Alexander Billioux, MD; DPhil, Souvik Chatterjee, MD; Idoreyin Montague, MD; Bennett Clark, MD; Andrew Hughes, MD; and Sanjay V. Desai, MD

BACKGROUND: Identifying hospitals that are both early and consistent adopters of high-value care can help shed light on the culture and practices at those institutions that are necessary to promote high-value care nationwide. The use of troponin testing to diagnose acute myocardial infarction (AMI), and not testing for myoglobin or creatine kinase-MB (CK-MB), is a high-value recommendation of the Choosing Wisely® campaign.

OBJECTIVE: To examine the variation in cardiac biomarker testing and the effect of the Choosing Wisely® troponin-only testing recommendation for the diagnosis of AMI.

DESIGN: A retrospective, observational study using administrative ordering data from Vizient’s Clinical Database/Resource Manager.

PATIENTS: Hospitalized patients with a principal discharge diagnosis of AMI.

INTERVENTION: The Choosing Wisely® recommendation to order troponin-only testing to diagnose AMI was released during the first quarter of 2015.

RESULTS: In 19 hospitals, troponin-only testing was consistently ordered to diagnose AMI before the Choosing Wisely® recommendation and throughout the study period. In 34 hospitals, both troponin testing and myoglobin/CK-MB testing were ordered to diagnose AMI even after the Choosing Wisely® recommendation. In 26 hospitals with low rates of troponin-only testing before the Choosing Wisely® recommendation, the release of the recommendation was associated with a statistically significant increase in the rate of troponin-only testing to diagnose AMI.

CONCLUSION: In institutions with low rates of troponin-only testing prior to the Choosing Wisely® recommendation, the recommendation was associated with a significant increase in the rate of troponin-only testing.

Read the entire article in the Dec. 2017 issue of the Journal of Hospital Medicine.

Also in JHM this month

Hospital perceptions of Medicare’s Sepsis Quality Reporting Initiative

AUTHORS: Ian J. Barbash, MD, MS; Kimberly J. Rak, PhD; Courtney C. Kuza, MPH; and Jeremy M. Kahn, MD, MS

Health literacy and hospital length of stay: An inpatient cohort study

AUTHORS: Ethan G. Jaffee, MD; Vineet M. Arora, MD, MAPP; Madeleine I. Matthiesen, MD; David O. Meltzer, MD, PhD, MHM; and Valerie G. Press, MD, FAAP, FACP, MPH

How exemplary teaching physicians interact with hospitalized patients

AUTHORS: Sanjay Saint, MD, MPH, FHM; Molly Harrod, PhD; Karen E. Fowler, MPH; and Nathan Houchens, MD, FACP, FHM

A randomized cohort controlled trial to compare intern sign-out training interventions

AUTHORS: Soo-Hoon Lee, PhD; Christopher Terndrup, MD; Phillip H. Phan, PhD; Sandra E. Zaeh, MD; Kwame Atsina, MD; Nicole Minkove, MD; Alexander Billioux, MD; DPhil, Souvik Chatterjee, MD; Idoreyin Montague, MD; Bennett Clark, MD; Andrew Hughes, MD; and Sanjay V. Desai, MD

LOS ANGELES – Michael Snyder, PhD, wears his research on his sleeve, so to speak. On any given day, he wears up to eight devices on his body that measure everything from radiation exposure to fasting glucose and sleep activity.

The way he sees it,wearables to monitor physiomes, plus personal omics profiling technology, give a high-resolution view of how health changes over periods of wellness and disease.

“We know intuitively that your health state is influenced by many things, including your genome and all of the things you’re exposed to, from pathogens to food, stress, and exercise,” Dr. Snyder said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They all impact your health state, but in a future not far away, people will be born with their genome sequenced, and we will understand in a probabilistic fashion how, with a set of variants in your genome, if you are exposed to certain environmental conditions, you will have certain health outcomes. As an example, if you’re at risk for Parkinson’s disease, you probably shouldn’t be a pesticide worker, because that greatly increases the chances by which you get Parkinson’s.”

About 8 years ago, he and his associates launched an ongoing longitudinal personal omics profiling project of 105 individuals, 55% of whom are prediabetic. After undergoing genome sequencing, each person undergoes measurement of 14 different omics every 3 months, including their RNA, proteins, lipidomics, cytokines, and microbiome (Cell Host Microbe. 2014 Sep 10;16[3]:276-89).

When a perturbation comes along, like a viral infection or positive results from a colonoscopy, the researchers gather additional samples. “We are trying to understand how the different omics relate to one another,” said Dr. Snyder, who in 2012 used his own genome sequence to predict and help diagnose his own type 2 diabetes, a story that received international media attention. “If you know the inputs into a system, you should be able to calculate the outputs, no matter how complex the system is. You should be able to make meaningful associations. In this case, the inputs are your genome, your epigenome and your microbiome, and the foods you eat. The outputs would be the metabolome, and things like that. We try to understand how responses to, say, viral infections or other perturbations are similar to one another, like congestion and fever, but also why some people get more ill than others, or have varying disease-specific symptoms.”

To date, Dr. Snyder and his associates have collected about 1,800 time points and roughly 10,000 samples. The first 1,000 of those time points have been analyzed. Of the first 70 people who underwent genome sequencing, 12 had pathogenic mutations that are clinically actionable, including mutations in BRCA1, which is associated with breast and ovarian cancer; APC and MUTYH, which are associated with colon cancer; SHBD, which is associated with a high frequency of neuroendocrine tumors; and RBM20, which is associated with dilated cardiomyopathy. One such person “underwent stress testing, and it turns out he does have a heart defect,” noted Dr. Snyder, who is also the author of Genomics and Personalized Medicine: What Everyone Needs to Know (New York: Oxford University Press, 2016). “So some of this information is extremely valuable. This is why we argue that genome sequencing, much like family history, will one day move into the clinic for those who want to use it.”

So far, the longitudinal personal omics analysis has revealed other important diagnoses that likely would have flown under the radar of conventional Western medicine, including a heart defect in one person that was detected by a simple wearable device, a case of early lymphoma, and a case of MGUS (monoclonal gammopathy of unknown significance), which is a precancerous condition.

“We have also had many metabolic cases; a lot of folks were prediabetic and others were diabetic,” Dr. Snyder said. “It’s hard to predict exactly what you’re going to see for any one person. But when you collect a lot of this data, you do find things that are important for their health.”

Of the current study participants, 23 underwent a dietary perturbation. Of these, 13 were insulin resistant and 10 were healthy controls, matched for body mass index. The subjects consumed an extra 1,000 calories per day for 30 days, maintained their peak weight for 7 days, and embarked on a weight loss program for 60 days. “We looked at the effects of weight gain and weight loss in incredible molecular detail,” Dr. Snyder explained, noting that the work will appear in a forthcoming edition of Cell Systems. “At baseline, we can tell the insulin-resistant from the -sensitive folks. After people gain and lose weight, we can identify all the compounds and biochemical pathways that change by using integrative c-means clustering to identify pattern recognition across RNA sequencing, proteome, metabolome, microbiome, and cytokines. From blood, we can actually see these compounds changing. We also can tease out differences between resistance and sensitivity in their reaction to weight gain and weight loss. For example, in the microbiome, the insulin-resistant folks were more resistant to changes in weight gain and weight loss, while insulin-sensitive folks go up and down pretty well.”

The researchers also observed that the omics profile of each person who participated in the dietary perturbation study was different at baseline. “So everybody is special, and not just to our mothers,” Dr. Snyder said. “That is to say, if I profile you, you will not look like anyone sitting next to you. If you go through a perturbation, you will still look more like you than the person sitting next to you.” Going forward, he predicted that personal omics profiling “will build a personal dashboard that relays into your smartphone and can measure your health. Just like your car dashboard, we hope that you’ll have indicators of health, which will be your command center of the future.”

He disclosed that he is a scientific adviser to Personalis, Genapsys, SensOmics, and Qbio.

[email protected]

LOS ANGELES – Michael Snyder, PhD, wears his research on his sleeve, so to speak. On any given day, he wears up to eight devices on his body that measure everything from radiation exposure to fasting glucose and sleep activity.

The way he sees it,wearables to monitor physiomes, plus personal omics profiling technology, give a high-resolution view of how health changes over periods of wellness and disease.

“We know intuitively that your health state is influenced by many things, including your genome and all of the things you’re exposed to, from pathogens to food, stress, and exercise,” Dr. Snyder said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They all impact your health state, but in a future not far away, people will be born with their genome sequenced, and we will understand in a probabilistic fashion how, with a set of variants in your genome, if you are exposed to certain environmental conditions, you will have certain health outcomes. As an example, if you’re at risk for Parkinson’s disease, you probably shouldn’t be a pesticide worker, because that greatly increases the chances by which you get Parkinson’s.”

About 8 years ago, he and his associates launched an ongoing longitudinal personal omics profiling project of 105 individuals, 55% of whom are prediabetic. After undergoing genome sequencing, each person undergoes measurement of 14 different omics every 3 months, including their RNA, proteins, lipidomics, cytokines, and microbiome (Cell Host Microbe. 2014 Sep 10;16[3]:276-89).

When a perturbation comes along, like a viral infection or positive results from a colonoscopy, the researchers gather additional samples. “We are trying to understand how the different omics relate to one another,” said Dr. Snyder, who in 2012 used his own genome sequence to predict and help diagnose his own type 2 diabetes, a story that received international media attention. “If you know the inputs into a system, you should be able to calculate the outputs, no matter how complex the system is. You should be able to make meaningful associations. In this case, the inputs are your genome, your epigenome and your microbiome, and the foods you eat. The outputs would be the metabolome, and things like that. We try to understand how responses to, say, viral infections or other perturbations are similar to one another, like congestion and fever, but also why some people get more ill than others, or have varying disease-specific symptoms.”

To date, Dr. Snyder and his associates have collected about 1,800 time points and roughly 10,000 samples. The first 1,000 of those time points have been analyzed. Of the first 70 people who underwent genome sequencing, 12 had pathogenic mutations that are clinically actionable, including mutations in BRCA1, which is associated with breast and ovarian cancer; APC and MUTYH, which are associated with colon cancer; SHBD, which is associated with a high frequency of neuroendocrine tumors; and RBM20, which is associated with dilated cardiomyopathy. One such person “underwent stress testing, and it turns out he does have a heart defect,” noted Dr. Snyder, who is also the author of Genomics and Personalized Medicine: What Everyone Needs to Know (New York: Oxford University Press, 2016). “So some of this information is extremely valuable. This is why we argue that genome sequencing, much like family history, will one day move into the clinic for those who want to use it.”

So far, the longitudinal personal omics analysis has revealed other important diagnoses that likely would have flown under the radar of conventional Western medicine, including a heart defect in one person that was detected by a simple wearable device, a case of early lymphoma, and a case of MGUS (monoclonal gammopathy of unknown significance), which is a precancerous condition.

“We have also had many metabolic cases; a lot of folks were prediabetic and others were diabetic,” Dr. Snyder said. “It’s hard to predict exactly what you’re going to see for any one person. But when you collect a lot of this data, you do find things that are important for their health.”

Of the current study participants, 23 underwent a dietary perturbation. Of these, 13 were insulin resistant and 10 were healthy controls, matched for body mass index. The subjects consumed an extra 1,000 calories per day for 30 days, maintained their peak weight for 7 days, and embarked on a weight loss program for 60 days. “We looked at the effects of weight gain and weight loss in incredible molecular detail,” Dr. Snyder explained, noting that the work will appear in a forthcoming edition of Cell Systems. “At baseline, we can tell the insulin-resistant from the -sensitive folks. After people gain and lose weight, we can identify all the compounds and biochemical pathways that change by using integrative c-means clustering to identify pattern recognition across RNA sequencing, proteome, metabolome, microbiome, and cytokines. From blood, we can actually see these compounds changing. We also can tease out differences between resistance and sensitivity in their reaction to weight gain and weight loss. For example, in the microbiome, the insulin-resistant folks were more resistant to changes in weight gain and weight loss, while insulin-sensitive folks go up and down pretty well.”

The researchers also observed that the omics profile of each person who participated in the dietary perturbation study was different at baseline. “So everybody is special, and not just to our mothers,” Dr. Snyder said. “That is to say, if I profile you, you will not look like anyone sitting next to you. If you go through a perturbation, you will still look more like you than the person sitting next to you.” Going forward, he predicted that personal omics profiling “will build a personal dashboard that relays into your smartphone and can measure your health. Just like your car dashboard, we hope that you’ll have indicators of health, which will be your command center of the future.”

He disclosed that he is a scientific adviser to Personalis, Genapsys, SensOmics, and Qbio.

[email protected]

LOS ANGELES – Michael Snyder, PhD, wears his research on his sleeve, so to speak. On any given day, he wears up to eight devices on his body that measure everything from radiation exposure to fasting glucose and sleep activity.

The way he sees it,wearables to monitor physiomes, plus personal omics profiling technology, give a high-resolution view of how health changes over periods of wellness and disease.

“We know intuitively that your health state is influenced by many things, including your genome and all of the things you’re exposed to, from pathogens to food, stress, and exercise,” Dr. Snyder said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They all impact your health state, but in a future not far away, people will be born with their genome sequenced, and we will understand in a probabilistic fashion how, with a set of variants in your genome, if you are exposed to certain environmental conditions, you will have certain health outcomes. As an example, if you’re at risk for Parkinson’s disease, you probably shouldn’t be a pesticide worker, because that greatly increases the chances by which you get Parkinson’s.”

About 8 years ago, he and his associates launched an ongoing longitudinal personal omics profiling project of 105 individuals, 55% of whom are prediabetic. After undergoing genome sequencing, each person undergoes measurement of 14 different omics every 3 months, including their RNA, proteins, lipidomics, cytokines, and microbiome (Cell Host Microbe. 2014 Sep 10;16[3]:276-89).

When a perturbation comes along, like a viral infection or positive results from a colonoscopy, the researchers gather additional samples. “We are trying to understand how the different omics relate to one another,” said Dr. Snyder, who in 2012 used his own genome sequence to predict and help diagnose his own type 2 diabetes, a story that received international media attention. “If you know the inputs into a system, you should be able to calculate the outputs, no matter how complex the system is. You should be able to make meaningful associations. In this case, the inputs are your genome, your epigenome and your microbiome, and the foods you eat. The outputs would be the metabolome, and things like that. We try to understand how responses to, say, viral infections or other perturbations are similar to one another, like congestion and fever, but also why some people get more ill than others, or have varying disease-specific symptoms.”

To date, Dr. Snyder and his associates have collected about 1,800 time points and roughly 10,000 samples. The first 1,000 of those time points have been analyzed. Of the first 70 people who underwent genome sequencing, 12 had pathogenic mutations that are clinically actionable, including mutations in BRCA1, which is associated with breast and ovarian cancer; APC and MUTYH, which are associated with colon cancer; SHBD, which is associated with a high frequency of neuroendocrine tumors; and RBM20, which is associated with dilated cardiomyopathy. One such person “underwent stress testing, and it turns out he does have a heart defect,” noted Dr. Snyder, who is also the author of Genomics and Personalized Medicine: What Everyone Needs to Know (New York: Oxford University Press, 2016). “So some of this information is extremely valuable. This is why we argue that genome sequencing, much like family history, will one day move into the clinic for those who want to use it.”

So far, the longitudinal personal omics analysis has revealed other important diagnoses that likely would have flown under the radar of conventional Western medicine, including a heart defect in one person that was detected by a simple wearable device, a case of early lymphoma, and a case of MGUS (monoclonal gammopathy of unknown significance), which is a precancerous condition.

“We have also had many metabolic cases; a lot of folks were prediabetic and others were diabetic,” Dr. Snyder said. “It’s hard to predict exactly what you’re going to see for any one person. But when you collect a lot of this data, you do find things that are important for their health.”

Of the current study participants, 23 underwent a dietary perturbation. Of these, 13 were insulin resistant and 10 were healthy controls, matched for body mass index. The subjects consumed an extra 1,000 calories per day for 30 days, maintained their peak weight for 7 days, and embarked on a weight loss program for 60 days. “We looked at the effects of weight gain and weight loss in incredible molecular detail,” Dr. Snyder explained, noting that the work will appear in a forthcoming edition of Cell Systems. “At baseline, we can tell the insulin-resistant from the -sensitive folks. After people gain and lose weight, we can identify all the compounds and biochemical pathways that change by using integrative c-means clustering to identify pattern recognition across RNA sequencing, proteome, metabolome, microbiome, and cytokines. From blood, we can actually see these compounds changing. We also can tease out differences between resistance and sensitivity in their reaction to weight gain and weight loss. For example, in the microbiome, the insulin-resistant folks were more resistant to changes in weight gain and weight loss, while insulin-sensitive folks go up and down pretty well.”

The researchers also observed that the omics profile of each person who participated in the dietary perturbation study was different at baseline. “So everybody is special, and not just to our mothers,” Dr. Snyder said. “That is to say, if I profile you, you will not look like anyone sitting next to you. If you go through a perturbation, you will still look more like you than the person sitting next to you.” Going forward, he predicted that personal omics profiling “will build a personal dashboard that relays into your smartphone and can measure your health. Just like your car dashboard, we hope that you’ll have indicators of health, which will be your command center of the future.”

He disclosed that he is a scientific adviser to Personalis, Genapsys, SensOmics, and Qbio.

[email protected]

The prevalence of rheumatoid arthritis, as well as thyroid disease and epilepsy, was significantly higher in children whose mothers had RA, according to data from a nationwide cohort study in Denmark.

RA runs in families, and many women with RA are concerned about the possible impact of their disease on a developing fetus, wrote Line R. Jølving of Odense (Denmark) University Hospital and the University of Southern Denmark in Odense and her colleagues in Arthritis Care & Research. “However, we do not have sufficient knowledge on the association between maternal RA and long-term chronic childhood outcomes, and still we do not know which specific chronic diseases to be especially aware of in children of women with RA,” they said.

Ryan McVay/ThinkStock

Overall, the risk of RA was almost three times as high for the children of mothers with RA (hazard ratio, 2.89) as it was for the children of women without RA. In addition, the risk of thyroid disease was more than twice as high (HR, 2.19), and the risk of epilepsy was more than 50% higher (HR, 1.61). Maternal RA during pregnancy had no significant impact on children’s anxiety and personality disorders or on the presence of chronic lung disease.

Mothers with RA were generally older than were those without the condition. The children of mothers with RA were significantly more likely to be born via cesarean section, preterm, and small for gestational age, the researchers said.

The results were limited by the potential inclusion of misclassified diagnoses of child outcomes and by the lack of data on medication use. In addition, the study was not designed to determine the effect of biologic mechanisms or genes, the researchers said. Despite these limitations, “the findings in this study are relevant for pediatricians, rheumatologists, and general practitioners in order to have special awareness of early symptoms of RA, thyroid disease, and epilepsy in offspring of mothers with RA,” they said.

The researchers had no financial conflicts to disclose. The study was funded by several sources, including the Region of Southern Denmark, the University of Southern Denmark in Odense, the Center for Clinical Epidemiology, Odense University Hospital, and the Colitis-Crohn Association in Denmark.

SOURCE: Jølving L et al. Arthritis Care Res. 2017 Dec 11. doi: 10.1002/acr.23461.

The prevalence of rheumatoid arthritis, as well as thyroid disease and epilepsy, was significantly higher in children whose mothers had RA, according to data from a nationwide cohort study in Denmark.

RA runs in families, and many women with RA are concerned about the possible impact of their disease on a developing fetus, wrote Line R. Jølving of Odense (Denmark) University Hospital and the University of Southern Denmark in Odense and her colleagues in Arthritis Care & Research. “However, we do not have sufficient knowledge on the association between maternal RA and long-term chronic childhood outcomes, and still we do not know which specific chronic diseases to be especially aware of in children of women with RA,” they said.

Ryan McVay/ThinkStock

Overall, the risk of RA was almost three times as high for the children of mothers with RA (hazard ratio, 2.89) as it was for the children of women without RA. In addition, the risk of thyroid disease was more than twice as high (HR, 2.19), and the risk of epilepsy was more than 50% higher (HR, 1.61). Maternal RA during pregnancy had no significant impact on children’s anxiety and personality disorders or on the presence of chronic lung disease.

Mothers with RA were generally older than were those without the condition. The children of mothers with RA were significantly more likely to be born via cesarean section, preterm, and small for gestational age, the researchers said.

The results were limited by the potential inclusion of misclassified diagnoses of child outcomes and by the lack of data on medication use. In addition, the study was not designed to determine the effect of biologic mechanisms or genes, the researchers said. Despite these limitations, “the findings in this study are relevant for pediatricians, rheumatologists, and general practitioners in order to have special awareness of early symptoms of RA, thyroid disease, and epilepsy in offspring of mothers with RA,” they said.

The researchers had no financial conflicts to disclose. The study was funded by several sources, including the Region of Southern Denmark, the University of Southern Denmark in Odense, the Center for Clinical Epidemiology, Odense University Hospital, and the Colitis-Crohn Association in Denmark.

SOURCE: Jølving L et al. Arthritis Care Res. 2017 Dec 11. doi: 10.1002/acr.23461.

The prevalence of rheumatoid arthritis, as well as thyroid disease and epilepsy, was significantly higher in children whose mothers had RA, according to data from a nationwide cohort study in Denmark.

RA runs in families, and many women with RA are concerned about the possible impact of their disease on a developing fetus, wrote Line R. Jølving of Odense (Denmark) University Hospital and the University of Southern Denmark in Odense and her colleagues in Arthritis Care & Research. “However, we do not have sufficient knowledge on the association between maternal RA and long-term chronic childhood outcomes, and still we do not know which specific chronic diseases to be especially aware of in children of women with RA,” they said.

Ryan McVay/ThinkStock

Overall, the risk of RA was almost three times as high for the children of mothers with RA (hazard ratio, 2.89) as it was for the children of women without RA. In addition, the risk of thyroid disease was more than twice as high (HR, 2.19), and the risk of epilepsy was more than 50% higher (HR, 1.61). Maternal RA during pregnancy had no significant impact on children’s anxiety and personality disorders or on the presence of chronic lung disease.

Mothers with RA were generally older than were those without the condition. The children of mothers with RA were significantly more likely to be born via cesarean section, preterm, and small for gestational age, the researchers said.

The results were limited by the potential inclusion of misclassified diagnoses of child outcomes and by the lack of data on medication use. In addition, the study was not designed to determine the effect of biologic mechanisms or genes, the researchers said. Despite these limitations, “the findings in this study are relevant for pediatricians, rheumatologists, and general practitioners in order to have special awareness of early symptoms of RA, thyroid disease, and epilepsy in offspring of mothers with RA,” they said.

The researchers had no financial conflicts to disclose. The study was funded by several sources, including the Region of Southern Denmark, the University of Southern Denmark in Odense, the Center for Clinical Epidemiology, Odense University Hospital, and the Colitis-Crohn Association in Denmark.

SOURCE: Jølving L et al. Arthritis Care Res. 2017 Dec 11. doi: 10.1002/acr.23461.

ANAHEIM, CALIF. – One-time infusion of cardiosphere-derived cells into the three major coronary arteries seemed to prevent and perhaps even reverse cardiac scarring, as well as improve arm function, in the open-label phase 1-2 HOPE-Duchenne trial of 25 boys with advanced Duchenne muscular dystrophy.

“Decreased scarring is really a big deal because this is counter to the natural history of Duchenne, where all the scars progress, senior investigator Ronald G. Victor, MD, said at the American Heart Association scientific sessions. “It was gratifying to see that the changes in scar coincided with improved regional systolic wall thickening, particularly in the inferior wall of the left ventricle, which is the very area disproportionately affected early and thus severely in Duchenne.”  

Glucocorticoids are the only thing that help to date, prolonging ambulation by about 3 years, but with Cushingoid features and other well-known side effects.

Cardiosphere-derived cells (CDCs) – cardiac progenitor cells – have shown some promise for heart failure. They don’t seem to engraft and grow, but rather to release extracellular vesicles packed with proteins, RNA, and other bioactive molecules. “They act as a role model to get endogenous cells to do the right thing. That’s what we think,” Dr. Victor said.

The HOPE-Duchenne trial [Halt Cardiomyopathy Progression in Duchenne] randomized 12 boys with Duchenne to usual care and 13 others to usual care plus a single infusion of 75 million CDCs divided equally among the left anterior descending, circumflex, and right coronary arteries. The cells were derived from donated heart muscle. The specific CDC preparation tested was “CAP-1002” from Capricor Therapeutics, the study’s sponsor.

The boys were aged 12-22 years, with a mean age of 17.8 years. They had left ventricle scarring in at least four MRI segments; their mean left ventricle ejection fraction was just below 50%; 68% were wheel-chair bound, and all were on stable steroid regimens.

At 12 months, cardiac scarring had increased about 5% in the control group, but decreased by about 7% in the treatment arm, although with no change ejection fraction improvement (P = .03).

Skeletal muscle was assessed by mid-level and distal performance of upper limb scoring, a measure of arm function developed specifically for Duchenne. “For patients who have lost ambulation, the ability to use a joystick to drive a scooter, the ability to feed themselves and use a computer and cellphone are absolutely key to quality of life,” he said.

At 12 months, performance of upper limb scores were largely unchanged in the control group, but improved in about half of the treated boys. “A couple were quite dramatic,” Dr. Victor said. The differences were statistically significant (P = .007) when limited to subjects who started with scores below 55 points, with 58 points meaning normal function.

On the safety side, nothing unusual happened in the control arm, except a femur fracture.

One boy in the treatment arm went into ventricular fibrillation during the diagnostic angiogram. Five had periprocedural atrial fibrillation. All 13 had periprocedural troponin elevations, versus two boys in the control group over the entire course of the study. Dr. Victor didn’t report any deaths, but safety concerns are probably why Capricor is shifting to intravenous infusion for the next trial, HOPE-2.

Dr. Victor noted that troponin leaks “wax and wane” over time in Duchenne, so the transient increases in the treatment arm “were superimposed on a baseline of abnormal cardiac enzymes.”

The Food and Drug Administration has green-lighted the company’s HOPE-2 trial to start enrollment in early 2018, with a larger number of patients and intravenous CDC delivery at 3 month intervals.

Several investigators were Capricor employees. Others were consultants or reported ownership interests. Dr. Victor was the principal investigator at Cedars-Sinai, and was on the trial’s steering committee. The University of Florida, Gainesville, and Cincinnati Children’s Hospital Medical Center, Ohio, were the other two study sites.

[email protected]

SOURCE: Ronald Victor, MD; 2017 AHA Scientific Sessions abstract number S1177

ANAHEIM, CALIF. – One-time infusion of cardiosphere-derived cells into the three major coronary arteries seemed to prevent and perhaps even reverse cardiac scarring, as well as improve arm function, in the open-label phase 1-2 HOPE-Duchenne trial of 25 boys with advanced Duchenne muscular dystrophy.

“Decreased scarring is really a big deal because this is counter to the natural history of Duchenne, where all the scars progress, senior investigator Ronald G. Victor, MD, said at the American Heart Association scientific sessions. “It was gratifying to see that the changes in scar coincided with improved regional systolic wall thickening, particularly in the inferior wall of the left ventricle, which is the very area disproportionately affected early and thus severely in Duchenne.”  

Glucocorticoids are the only thing that help to date, prolonging ambulation by about 3 years, but with Cushingoid features and other well-known side effects.

Cardiosphere-derived cells (CDCs) – cardiac progenitor cells – have shown some promise for heart failure. They don’t seem to engraft and grow, but rather to release extracellular vesicles packed with proteins, RNA, and other bioactive molecules. “They act as a role model to get endogenous cells to do the right thing. That’s what we think,” Dr. Victor said.

The HOPE-Duchenne trial [Halt Cardiomyopathy Progression in Duchenne] randomized 12 boys with Duchenne to usual care and 13 others to usual care plus a single infusion of 75 million CDCs divided equally among the left anterior descending, circumflex, and right coronary arteries. The cells were derived from donated heart muscle. The specific CDC preparation tested was “CAP-1002” from Capricor Therapeutics, the study’s sponsor.

The boys were aged 12-22 years, with a mean age of 17.8 years. They had left ventricle scarring in at least four MRI segments; their mean left ventricle ejection fraction was just below 50%; 68% were wheel-chair bound, and all were on stable steroid regimens.

At 12 months, cardiac scarring had increased about 5% in the control group, but decreased by about 7% in the treatment arm, although with no change ejection fraction improvement (P = .03).

Skeletal muscle was assessed by mid-level and distal performance of upper limb scoring, a measure of arm function developed specifically for Duchenne. “For patients who have lost ambulation, the ability to use a joystick to drive a scooter, the ability to feed themselves and use a computer and cellphone are absolutely key to quality of life,” he said.

At 12 months, performance of upper limb scores were largely unchanged in the control group, but improved in about half of the treated boys. “A couple were quite dramatic,” Dr. Victor said. The differences were statistically significant (P = .007) when limited to subjects who started with scores below 55 points, with 58 points meaning normal function.

On the safety side, nothing unusual happened in the control arm, except a femur fracture.

One boy in the treatment arm went into ventricular fibrillation during the diagnostic angiogram. Five had periprocedural atrial fibrillation. All 13 had periprocedural troponin elevations, versus two boys in the control group over the entire course of the study. Dr. Victor didn’t report any deaths, but safety concerns are probably why Capricor is shifting to intravenous infusion for the next trial, HOPE-2.

Dr. Victor noted that troponin leaks “wax and wane” over time in Duchenne, so the transient increases in the treatment arm “were superimposed on a baseline of abnormal cardiac enzymes.”

The Food and Drug Administration has green-lighted the company’s HOPE-2 trial to start enrollment in early 2018, with a larger number of patients and intravenous CDC delivery at 3 month intervals.

Several investigators were Capricor employees. Others were consultants or reported ownership interests. Dr. Victor was the principal investigator at Cedars-Sinai, and was on the trial’s steering committee. The University of Florida, Gainesville, and Cincinnati Children’s Hospital Medical Center, Ohio, were the other two study sites.

[email protected]

SOURCE: Ronald Victor, MD; 2017 AHA Scientific Sessions abstract number S1177

ANAHEIM, CALIF. – One-time infusion of cardiosphere-derived cells into the three major coronary arteries seemed to prevent and perhaps even reverse cardiac scarring, as well as improve arm function, in the open-label phase 1-2 HOPE-Duchenne trial of 25 boys with advanced Duchenne muscular dystrophy.

“Decreased scarring is really a big deal because this is counter to the natural history of Duchenne, where all the scars progress, senior investigator Ronald G. Victor, MD, said at the American Heart Association scientific sessions. “It was gratifying to see that the changes in scar coincided with improved regional systolic wall thickening, particularly in the inferior wall of the left ventricle, which is the very area disproportionately affected early and thus severely in Duchenne.”  

Glucocorticoids are the only thing that help to date, prolonging ambulation by about 3 years, but with Cushingoid features and other well-known side effects.

Cardiosphere-derived cells (CDCs) – cardiac progenitor cells – have shown some promise for heart failure. They don’t seem to engraft and grow, but rather to release extracellular vesicles packed with proteins, RNA, and other bioactive molecules. “They act as a role model to get endogenous cells to do the right thing. That’s what we think,” Dr. Victor said.

The HOPE-Duchenne trial [Halt Cardiomyopathy Progression in Duchenne] randomized 12 boys with Duchenne to usual care and 13 others to usual care plus a single infusion of 75 million CDCs divided equally among the left anterior descending, circumflex, and right coronary arteries. The cells were derived from donated heart muscle. The specific CDC preparation tested was “CAP-1002” from Capricor Therapeutics, the study’s sponsor.

The boys were aged 12-22 years, with a mean age of 17.8 years. They had left ventricle scarring in at least four MRI segments; their mean left ventricle ejection fraction was just below 50%; 68% were wheel-chair bound, and all were on stable steroid regimens.

At 12 months, cardiac scarring had increased about 5% in the control group, but decreased by about 7% in the treatment arm, although with no change ejection fraction improvement (P = .03).

Skeletal muscle was assessed by mid-level and distal performance of upper limb scoring, a measure of arm function developed specifically for Duchenne. “For patients who have lost ambulation, the ability to use a joystick to drive a scooter, the ability to feed themselves and use a computer and cellphone are absolutely key to quality of life,” he said.

At 12 months, performance of upper limb scores were largely unchanged in the control group, but improved in about half of the treated boys. “A couple were quite dramatic,” Dr. Victor said. The differences were statistically significant (P = .007) when limited to subjects who started with scores below 55 points, with 58 points meaning normal function.

On the safety side, nothing unusual happened in the control arm, except a femur fracture.

One boy in the treatment arm went into ventricular fibrillation during the diagnostic angiogram. Five had periprocedural atrial fibrillation. All 13 had periprocedural troponin elevations, versus two boys in the control group over the entire course of the study. Dr. Victor didn’t report any deaths, but safety concerns are probably why Capricor is shifting to intravenous infusion for the next trial, HOPE-2.

Dr. Victor noted that troponin leaks “wax and wane” over time in Duchenne, so the transient increases in the treatment arm “were superimposed on a baseline of abnormal cardiac enzymes.”

The Food and Drug Administration has green-lighted the company’s HOPE-2 trial to start enrollment in early 2018, with a larger number of patients and intravenous CDC delivery at 3 month intervals.

Several investigators were Capricor employees. Others were consultants or reported ownership interests. Dr. Victor was the principal investigator at Cedars-Sinai, and was on the trial’s steering committee. The University of Florida, Gainesville, and Cincinnati Children’s Hospital Medical Center, Ohio, were the other two study sites.

[email protected]

SOURCE: Ronald Victor, MD; 2017 AHA Scientific Sessions abstract number S1177